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Mood changes reported in cases of methotrexate use for dermatologic disease
, said Trisha Bhat and Carrie C. Coughlin, MD, both of Washington University, St. Louis.
Neurotoxicity with low-dose methotrexate often has been described when used to treat rheumatologic disease, the investigators said, but not in the dermatologic literature – although CNS symptoms such as dizziness and headache have been described in both.
An 8-year-old girl with psoriasis vulgaris and no prior psychiatric history began weekly subcutaneous methotrexate 12.5 mg (0.23 mg/kg) with folic acid supplementation 6 days per week after failing topical therapy. Her parents noticed severe irritability right away and fluctuating mood changes over the next 2 months. At first, she was angry and unsettled, with depressed mood; her irritability became less frequent later, but she said she wanted to hurt someone else. After stopping methotrexate, her mood returned to normal within 2 weeks.
It is unclear how methotrexate affects mood, but recent evidence suggests that abnormalities in synaptic plasticity are involved in mood changes, and there is evidence that mice treated with methotrexate show changes in synaptic plasticity. Methotrexate also increases extracellular adenosine, which affects neuronal excitability and synaptic plasticity, Ms. Bhat and Dr. Coughlin observed. Methotrexate also affects glucose metabolism in rats, and regional metabolic disturbances occur in a number of psychiatric disorders.
Read more at Pediatric Dermatology (2018 Jan 9. doi: 10.1111/pde.13406).
, said Trisha Bhat and Carrie C. Coughlin, MD, both of Washington University, St. Louis.
Neurotoxicity with low-dose methotrexate often has been described when used to treat rheumatologic disease, the investigators said, but not in the dermatologic literature – although CNS symptoms such as dizziness and headache have been described in both.
An 8-year-old girl with psoriasis vulgaris and no prior psychiatric history began weekly subcutaneous methotrexate 12.5 mg (0.23 mg/kg) with folic acid supplementation 6 days per week after failing topical therapy. Her parents noticed severe irritability right away and fluctuating mood changes over the next 2 months. At first, she was angry and unsettled, with depressed mood; her irritability became less frequent later, but she said she wanted to hurt someone else. After stopping methotrexate, her mood returned to normal within 2 weeks.
It is unclear how methotrexate affects mood, but recent evidence suggests that abnormalities in synaptic plasticity are involved in mood changes, and there is evidence that mice treated with methotrexate show changes in synaptic plasticity. Methotrexate also increases extracellular adenosine, which affects neuronal excitability and synaptic plasticity, Ms. Bhat and Dr. Coughlin observed. Methotrexate also affects glucose metabolism in rats, and regional metabolic disturbances occur in a number of psychiatric disorders.
Read more at Pediatric Dermatology (2018 Jan 9. doi: 10.1111/pde.13406).
, said Trisha Bhat and Carrie C. Coughlin, MD, both of Washington University, St. Louis.
Neurotoxicity with low-dose methotrexate often has been described when used to treat rheumatologic disease, the investigators said, but not in the dermatologic literature – although CNS symptoms such as dizziness and headache have been described in both.
An 8-year-old girl with psoriasis vulgaris and no prior psychiatric history began weekly subcutaneous methotrexate 12.5 mg (0.23 mg/kg) with folic acid supplementation 6 days per week after failing topical therapy. Her parents noticed severe irritability right away and fluctuating mood changes over the next 2 months. At first, she was angry and unsettled, with depressed mood; her irritability became less frequent later, but she said she wanted to hurt someone else. After stopping methotrexate, her mood returned to normal within 2 weeks.
It is unclear how methotrexate affects mood, but recent evidence suggests that abnormalities in synaptic plasticity are involved in mood changes, and there is evidence that mice treated with methotrexate show changes in synaptic plasticity. Methotrexate also increases extracellular adenosine, which affects neuronal excitability and synaptic plasticity, Ms. Bhat and Dr. Coughlin observed. Methotrexate also affects glucose metabolism in rats, and regional metabolic disturbances occur in a number of psychiatric disorders.
Read more at Pediatric Dermatology (2018 Jan 9. doi: 10.1111/pde.13406).
FROM PEDIATRIC DERMATOLOGY
Clinical rule decreased pediatric trauma CT scans
ORLANDO – A according to a study presented at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.
With values for five clinical variables, the prediction rule would eliminate the need to subject some patients to unwarranted radiation exposure, which has become a growing health and financial concern for medical institutions.
“CT utilization rates in pediatric blunt trauma are very high, at a rate of 40%-60%, despite a relatively low incidence of intra-abdominal injury after abdominal trauma,” according to presenter Chase A. Arbra, MD, of the department of surgery at the Medical University of South Carolina, Charleston. “With increasing concerns regarding the cost and radiation exposure in children, our group is focusing on research to safely avoid these unnecessary scans.”
The rule, developed by the Pediatric Surgery Research Collaborative (PedSRC), evaluates abdominal wall trauma and tenderness, complaint of abdominal pain, aspartate aminotransferase level greater than 200 U/L, abnormal pancreatic enzymes, and abnormal chest x-rays to determine a patient’s risk of having an intra-abdominal injury (IAI). If none of the five variables in a patient is abnormal, the finding is considered negative and the patient is considered to be at very low risk for having an IAI or an IAI requiring acute intervention (IAI-I).
Investigators studied 2,435 pediatric blunt trauma patients with all five clinical variables documented within 6 hours of arrival, using data gathered from the Pediatric Emergency Care Applied Research Network.
Patients were an average of 9.4 years old, with an IAI rate of 9.7% (n = 235) and an IAI-I rate of 2.5% (n = 60); 61.1% of the patients had a CT scan.
Prediction sensitivity of the method was 97.5% for IAI and 100% for IAI-I, said Dr. Arbra. Negative predictive value for the model was 99.3% for IAI and 100% for IAI-I.
Patients who were found to have aspartate aminotransferase level greater than 200 U/L were at the highest risk of IAI (52.6%) and IAI-I (11.9%), according to investigators. One-third of the test population was found to be at very low risk after using the prediction model, according to Dr. Arbra, with 46.8% of them still undergoing a CT scan. Of those tested, six patients had IAI that was not predicted by the model, three of whom were intubated. Because CT scans were not required and there was no follow-up after discharge, investigators are not able to determine if any minor IAI was missed.
Despite these limitations, the highly sensitive rule shows great promise, according to Dr. Arbra.
“Patients with 0-5 variables, even patients who were involved in a high impact mechanism, could potentially forgo CT scans safely.”
A closer look at the 26 patients who only had abdominal pain showed that only 1 had IAI, suggesting that patients with only abdominal pain could be safely observed with only serial exams, according to Dr. Arbra.
Investigators plan to conduct a prospective study that will include older patients.
Dr. Arbra concluded, “The rule could potentially help centers to determine who could avoid imaging prior to transfer and potentially could one day be used to see who could be discharged.”
Dr. Arbra reported no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
SOURCE: Arbra CA. EAST Scientific Assembly 2018, paper #7.
ORLANDO – A according to a study presented at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.
With values for five clinical variables, the prediction rule would eliminate the need to subject some patients to unwarranted radiation exposure, which has become a growing health and financial concern for medical institutions.
“CT utilization rates in pediatric blunt trauma are very high, at a rate of 40%-60%, despite a relatively low incidence of intra-abdominal injury after abdominal trauma,” according to presenter Chase A. Arbra, MD, of the department of surgery at the Medical University of South Carolina, Charleston. “With increasing concerns regarding the cost and radiation exposure in children, our group is focusing on research to safely avoid these unnecessary scans.”
The rule, developed by the Pediatric Surgery Research Collaborative (PedSRC), evaluates abdominal wall trauma and tenderness, complaint of abdominal pain, aspartate aminotransferase level greater than 200 U/L, abnormal pancreatic enzymes, and abnormal chest x-rays to determine a patient’s risk of having an intra-abdominal injury (IAI). If none of the five variables in a patient is abnormal, the finding is considered negative and the patient is considered to be at very low risk for having an IAI or an IAI requiring acute intervention (IAI-I).
Investigators studied 2,435 pediatric blunt trauma patients with all five clinical variables documented within 6 hours of arrival, using data gathered from the Pediatric Emergency Care Applied Research Network.
Patients were an average of 9.4 years old, with an IAI rate of 9.7% (n = 235) and an IAI-I rate of 2.5% (n = 60); 61.1% of the patients had a CT scan.
Prediction sensitivity of the method was 97.5% for IAI and 100% for IAI-I, said Dr. Arbra. Negative predictive value for the model was 99.3% for IAI and 100% for IAI-I.
Patients who were found to have aspartate aminotransferase level greater than 200 U/L were at the highest risk of IAI (52.6%) and IAI-I (11.9%), according to investigators. One-third of the test population was found to be at very low risk after using the prediction model, according to Dr. Arbra, with 46.8% of them still undergoing a CT scan. Of those tested, six patients had IAI that was not predicted by the model, three of whom were intubated. Because CT scans were not required and there was no follow-up after discharge, investigators are not able to determine if any minor IAI was missed.
Despite these limitations, the highly sensitive rule shows great promise, according to Dr. Arbra.
“Patients with 0-5 variables, even patients who were involved in a high impact mechanism, could potentially forgo CT scans safely.”
A closer look at the 26 patients who only had abdominal pain showed that only 1 had IAI, suggesting that patients with only abdominal pain could be safely observed with only serial exams, according to Dr. Arbra.
Investigators plan to conduct a prospective study that will include older patients.
Dr. Arbra concluded, “The rule could potentially help centers to determine who could avoid imaging prior to transfer and potentially could one day be used to see who could be discharged.”
Dr. Arbra reported no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
SOURCE: Arbra CA. EAST Scientific Assembly 2018, paper #7.
ORLANDO – A according to a study presented at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.
With values for five clinical variables, the prediction rule would eliminate the need to subject some patients to unwarranted radiation exposure, which has become a growing health and financial concern for medical institutions.
“CT utilization rates in pediatric blunt trauma are very high, at a rate of 40%-60%, despite a relatively low incidence of intra-abdominal injury after abdominal trauma,” according to presenter Chase A. Arbra, MD, of the department of surgery at the Medical University of South Carolina, Charleston. “With increasing concerns regarding the cost and radiation exposure in children, our group is focusing on research to safely avoid these unnecessary scans.”
The rule, developed by the Pediatric Surgery Research Collaborative (PedSRC), evaluates abdominal wall trauma and tenderness, complaint of abdominal pain, aspartate aminotransferase level greater than 200 U/L, abnormal pancreatic enzymes, and abnormal chest x-rays to determine a patient’s risk of having an intra-abdominal injury (IAI). If none of the five variables in a patient is abnormal, the finding is considered negative and the patient is considered to be at very low risk for having an IAI or an IAI requiring acute intervention (IAI-I).
Investigators studied 2,435 pediatric blunt trauma patients with all five clinical variables documented within 6 hours of arrival, using data gathered from the Pediatric Emergency Care Applied Research Network.
Patients were an average of 9.4 years old, with an IAI rate of 9.7% (n = 235) and an IAI-I rate of 2.5% (n = 60); 61.1% of the patients had a CT scan.
Prediction sensitivity of the method was 97.5% for IAI and 100% for IAI-I, said Dr. Arbra. Negative predictive value for the model was 99.3% for IAI and 100% for IAI-I.
Patients who were found to have aspartate aminotransferase level greater than 200 U/L were at the highest risk of IAI (52.6%) and IAI-I (11.9%), according to investigators. One-third of the test population was found to be at very low risk after using the prediction model, according to Dr. Arbra, with 46.8% of them still undergoing a CT scan. Of those tested, six patients had IAI that was not predicted by the model, three of whom were intubated. Because CT scans were not required and there was no follow-up after discharge, investigators are not able to determine if any minor IAI was missed.
Despite these limitations, the highly sensitive rule shows great promise, according to Dr. Arbra.
“Patients with 0-5 variables, even patients who were involved in a high impact mechanism, could potentially forgo CT scans safely.”
A closer look at the 26 patients who only had abdominal pain showed that only 1 had IAI, suggesting that patients with only abdominal pain could be safely observed with only serial exams, according to Dr. Arbra.
Investigators plan to conduct a prospective study that will include older patients.
Dr. Arbra concluded, “The rule could potentially help centers to determine who could avoid imaging prior to transfer and potentially could one day be used to see who could be discharged.”
Dr. Arbra reported no relevant financial disclosures.
ezimmerman@frontlinemedcom.com
SOURCE: Arbra CA. EAST Scientific Assembly 2018, paper #7.
REPORTING FROM EAST 2018
Key clinical point: New prediction model successfully identified patients with intra-abdominal injury (IAI) and IAI patients who require acute intervention (IAI-I).
Major finding: The test had a negative predictive value of 99.3% in IAI patients and 100% in IAI-I patients when either had no abnormalities.
Study details: Prospective study of 2,345 pediatric patients with IAI or IAI-I, the data for which was collected from the Pediatric Emergency Care Applied Research Network.
Disclosures: Dr. Arbra reported no relevant financial disclosures.
Source: Arbra CA. EAST Scientific Assembly 2018, paper #7.
Pathological video game use can be ‘life-dominating’
SAN DIEGO – As a medical student, David L. Atkinson, MD, learned about a group of five adult men who played EverQuest, which bills itself as a 3D online world that “offers endless excitement, adventure, battle, and discovery.” They shared an apartment in Austin, Tex., and rotated which one would hold a full-time job while the other four spent their waking hours playing EverQuest.
“It was a little concerning,” recalled Dr. Atkinson, now a psychiatrist and the medical director of the teen recovery program at Children’s Health, Dallas. “EverQuest had a button in the game where you could order a pizza without interrupting your game play. Pathological video game use can be incredibly life-dominating.”
Many terms are used for pathological video game use, including problematic video game use, gaming disorder, and Internet gaming disorder, which is the term used in section III of DSM-5. Whether chronic video game use is a societal problem or an individual problem “is a very big question,” Dr. Atkinson said. “When we look at some of the prevalence data from Monitoring the Future, we have seen reductions in all kinds of substance use. We have seen reductions in teenage motor vehicle accidents and in teen pregnancy. If kids are playing video games and they’re all getting out of shape, that’s a cultural challenge. A clinician, though, may advocate against it as part of good health care.
“For instance, underage drinking in some American subcultures is normative. It doesn’t mean it’s a good idea.”
Most youth do not develop addictive behavior from playing games like EverQuest. “Substance use and gaming are different,” Dr. Atkinson said. “The amount of time spent at the expense of other things is one of the primary harms of video gaming, but financial concerns are not irrelevant. The new Star Wars Battlefront game would cost $2,100 if someone were to buy all of the available extras for the video game. Otherwise, it would take several hundred hours of game play to achieve all of these unlocked features.” While video games do not induce supraphysiologic dopamine release in the way drugs like cocaine do, the addictive potential is measured by an equation of reward versus effort. Obtaining a video game is not dependent upon social interactions, unlike drug use in states where the drug in question is illegal. In fact, the fewer social connections, the greater the risk of developing a video game use disorder.
“The perception of harm of video game addiction is very low, and parents do not consider the potential for developing an addiction before they buy a computer, handheld device, or video game console,” he said. “It is viewed as something that has to be limited ... not as something that is impossible to limit.” However, when parents begin to detect problems, they often find themselves unable to control their children’s or teens’ use of gaming, according to Dr. Atkinson.
In the DSM-5, Internet gaming disorder is defined as being preoccupied with games and withdrawn when not playing them, including irritability, anxiety, and sadness. Tolerance manifests as needing to spend more time playing the game. Typically, gamers cannot reduce their use despite effort, and there is a loss of interest in other activities and hobbies, Dr. Atkinson said. They may continue to engage in overuse of games despite knowing it’s a problem; they may lie about usage, may use games to escape anxiety or guilt, and may have lost or risked lose or risk relationships or career opportunities because of games.
“Not all gamers will do all of these things,” he emphasized. “For example, some gamers have disordered use and lose interest in other things, but don’t lie about it.” DSM-5 criteria also note that the video gaming itself must cause clinically significant impairment and must not be a manifestation of another disorder.
Tools aimed at helping in the diagnosis include the Problem Video Game Playing Questionnaire, the Internet Gaming Disorder Scale, the Internet Gaming Disorder Scale–Short-Form, the Problematic Online Gaming Questionnaire, the Game Addiction Scale, and the Electronic Gaming Motives Questionnaire, which measures enhancement, coping, social, and self-gratification motives.
According to Dr. Atkinson, 90% of children in Japan, Korea, North America, and Europe play video games. However, the prevalence of Internet gaming disorder is estimated to be 1% in the United States, 1.14% in Germany, and 5.9% in South Korea. Males have higher rates of pathological video game use, while afflicted females tend to have more problems. Pathological gaming use is associated with high levels of previous truancy and few leisure activities. It’s also associated with depression, poor impulse control, narcissistic traits, high anxiety, poor social competence, and less religiosity.
“The overlap with depression is very interesting,” Dr. Atkinson said. “ When they get rejected in a peer group or for a job, they tend to take it harder than people who don’t game. The gaming world is a place where you can be safe from rejection. If your credit card goes through, you’re allowed in.”
Anhedonia is another factor within the clinical syndrome of depression that is associated with video game use. A nationwide community sample of individuals in Korea showed that gaming and depression have their overlap most strongly with the “escape from negative emotions” model (J Nerv Ment Dis. 2017;205[7]:568-73). Other associated problems include greater obesity; metabolic indicators, such as high triglycerides and cholesterol; and sleep deprivation. Chronic gamers also tend to have less social support, less health promotion, and heightened social phobia. “When you’re gaming all the time, you’re going to have less opportunity to engage in an exposure paradigm to help you get over your social phobia,” Dr. Atkinson said. “Problem gamers are also more likely to have pathological use of pornography, poor impulse control, and ADHD symptoms.”
Studies of biobehavioral characteristics of those with pathological video game use suggest that there is a decreased dopamine striatal response (Neurosci Biobehav Rev. 2017 Apr;75:314-30). They also suggest decreased functional connectivity across areas of the brain, including decreased resting-state functional connectivity between ventral tegmental area and the nucleus accumbens, and lower tonic dopamine firing.
Parental management training can be successful at setting gaming limits in children under 12 years of age, he said. Pathological video game use is associated with physiologic stress in the family problem-solving task. One study of a brief 3-week family therapy intervention as measured by functional MRI showed that improvement in perceived family cohesion was associated with an increase in the activity of the caudate nucleus in response to the gamer’s viewing images of family cohesion and was inversely correlated with changes in online game playing time (Psychiatry Res. 2012 May 31;202[2]:126-31). “Bringing the family together may give them something to do besides gaming,” Dr. Atkinson said. “That can help them put games in a more balanced perspective.”
The largest evidence base supports cognitive-behavioral therapy for Internet gaming disorder, but there is insufficient evidence to make a clear statement of benefit (Clin Psychol Rev. 2017 Jun;54:123-33). Gaming-related cognitions accounted for a large portion of the variance in treatment response.
“Does the gaming cause the thoughts? Or do the thoughts cause the gaming?” Dr. Atkinson asked. “The cognitive model of CBT would tell you there’s a bidirectional relationship.”
As for medications, bupropion has been shown to reduce online gaming in depressed individuals, and escitalopram also may be efficacious. One comparative analysis showed that there were greater effects from using bupropion than for using escitalopram (Clin Psychopharmacol Neurosci. 2017 Nov 30;15[4]:361-8). Methylphenidate also has been shown to reduce online gaming (Compr Psychiatry. 2009 May-Jun;50[3]:251-6).
Parents who take video games away from their children often are met with a burst of aggression. “There’s an attempt to reestablish dominance in the situation, to obtain the old reinforcer or to reestablish control,” Dr. Atkinson said. “It’s different from tapering a drug; this is something that you have to plan for. Tapering video games is difficult to do. If the kid plays longer than they’re supposed to, what do you do then? You may have a fight to discontinue the video game. That’s one of the practical problems.”
Dr. Atkinson reported having no financial disclosures.
SOURCE: Atkinson DL. AAAP 2017.
SAN DIEGO – As a medical student, David L. Atkinson, MD, learned about a group of five adult men who played EverQuest, which bills itself as a 3D online world that “offers endless excitement, adventure, battle, and discovery.” They shared an apartment in Austin, Tex., and rotated which one would hold a full-time job while the other four spent their waking hours playing EverQuest.
“It was a little concerning,” recalled Dr. Atkinson, now a psychiatrist and the medical director of the teen recovery program at Children’s Health, Dallas. “EverQuest had a button in the game where you could order a pizza without interrupting your game play. Pathological video game use can be incredibly life-dominating.”
Many terms are used for pathological video game use, including problematic video game use, gaming disorder, and Internet gaming disorder, which is the term used in section III of DSM-5. Whether chronic video game use is a societal problem or an individual problem “is a very big question,” Dr. Atkinson said. “When we look at some of the prevalence data from Monitoring the Future, we have seen reductions in all kinds of substance use. We have seen reductions in teenage motor vehicle accidents and in teen pregnancy. If kids are playing video games and they’re all getting out of shape, that’s a cultural challenge. A clinician, though, may advocate against it as part of good health care.
“For instance, underage drinking in some American subcultures is normative. It doesn’t mean it’s a good idea.”
Most youth do not develop addictive behavior from playing games like EverQuest. “Substance use and gaming are different,” Dr. Atkinson said. “The amount of time spent at the expense of other things is one of the primary harms of video gaming, but financial concerns are not irrelevant. The new Star Wars Battlefront game would cost $2,100 if someone were to buy all of the available extras for the video game. Otherwise, it would take several hundred hours of game play to achieve all of these unlocked features.” While video games do not induce supraphysiologic dopamine release in the way drugs like cocaine do, the addictive potential is measured by an equation of reward versus effort. Obtaining a video game is not dependent upon social interactions, unlike drug use in states where the drug in question is illegal. In fact, the fewer social connections, the greater the risk of developing a video game use disorder.
“The perception of harm of video game addiction is very low, and parents do not consider the potential for developing an addiction before they buy a computer, handheld device, or video game console,” he said. “It is viewed as something that has to be limited ... not as something that is impossible to limit.” However, when parents begin to detect problems, they often find themselves unable to control their children’s or teens’ use of gaming, according to Dr. Atkinson.
In the DSM-5, Internet gaming disorder is defined as being preoccupied with games and withdrawn when not playing them, including irritability, anxiety, and sadness. Tolerance manifests as needing to spend more time playing the game. Typically, gamers cannot reduce their use despite effort, and there is a loss of interest in other activities and hobbies, Dr. Atkinson said. They may continue to engage in overuse of games despite knowing it’s a problem; they may lie about usage, may use games to escape anxiety or guilt, and may have lost or risked lose or risk relationships or career opportunities because of games.
“Not all gamers will do all of these things,” he emphasized. “For example, some gamers have disordered use and lose interest in other things, but don’t lie about it.” DSM-5 criteria also note that the video gaming itself must cause clinically significant impairment and must not be a manifestation of another disorder.
Tools aimed at helping in the diagnosis include the Problem Video Game Playing Questionnaire, the Internet Gaming Disorder Scale, the Internet Gaming Disorder Scale–Short-Form, the Problematic Online Gaming Questionnaire, the Game Addiction Scale, and the Electronic Gaming Motives Questionnaire, which measures enhancement, coping, social, and self-gratification motives.
According to Dr. Atkinson, 90% of children in Japan, Korea, North America, and Europe play video games. However, the prevalence of Internet gaming disorder is estimated to be 1% in the United States, 1.14% in Germany, and 5.9% in South Korea. Males have higher rates of pathological video game use, while afflicted females tend to have more problems. Pathological gaming use is associated with high levels of previous truancy and few leisure activities. It’s also associated with depression, poor impulse control, narcissistic traits, high anxiety, poor social competence, and less religiosity.
“The overlap with depression is very interesting,” Dr. Atkinson said. “ When they get rejected in a peer group or for a job, they tend to take it harder than people who don’t game. The gaming world is a place where you can be safe from rejection. If your credit card goes through, you’re allowed in.”
Anhedonia is another factor within the clinical syndrome of depression that is associated with video game use. A nationwide community sample of individuals in Korea showed that gaming and depression have their overlap most strongly with the “escape from negative emotions” model (J Nerv Ment Dis. 2017;205[7]:568-73). Other associated problems include greater obesity; metabolic indicators, such as high triglycerides and cholesterol; and sleep deprivation. Chronic gamers also tend to have less social support, less health promotion, and heightened social phobia. “When you’re gaming all the time, you’re going to have less opportunity to engage in an exposure paradigm to help you get over your social phobia,” Dr. Atkinson said. “Problem gamers are also more likely to have pathological use of pornography, poor impulse control, and ADHD symptoms.”
Studies of biobehavioral characteristics of those with pathological video game use suggest that there is a decreased dopamine striatal response (Neurosci Biobehav Rev. 2017 Apr;75:314-30). They also suggest decreased functional connectivity across areas of the brain, including decreased resting-state functional connectivity between ventral tegmental area and the nucleus accumbens, and lower tonic dopamine firing.
Parental management training can be successful at setting gaming limits in children under 12 years of age, he said. Pathological video game use is associated with physiologic stress in the family problem-solving task. One study of a brief 3-week family therapy intervention as measured by functional MRI showed that improvement in perceived family cohesion was associated with an increase in the activity of the caudate nucleus in response to the gamer’s viewing images of family cohesion and was inversely correlated with changes in online game playing time (Psychiatry Res. 2012 May 31;202[2]:126-31). “Bringing the family together may give them something to do besides gaming,” Dr. Atkinson said. “That can help them put games in a more balanced perspective.”
The largest evidence base supports cognitive-behavioral therapy for Internet gaming disorder, but there is insufficient evidence to make a clear statement of benefit (Clin Psychol Rev. 2017 Jun;54:123-33). Gaming-related cognitions accounted for a large portion of the variance in treatment response.
“Does the gaming cause the thoughts? Or do the thoughts cause the gaming?” Dr. Atkinson asked. “The cognitive model of CBT would tell you there’s a bidirectional relationship.”
As for medications, bupropion has been shown to reduce online gaming in depressed individuals, and escitalopram also may be efficacious. One comparative analysis showed that there were greater effects from using bupropion than for using escitalopram (Clin Psychopharmacol Neurosci. 2017 Nov 30;15[4]:361-8). Methylphenidate also has been shown to reduce online gaming (Compr Psychiatry. 2009 May-Jun;50[3]:251-6).
Parents who take video games away from their children often are met with a burst of aggression. “There’s an attempt to reestablish dominance in the situation, to obtain the old reinforcer or to reestablish control,” Dr. Atkinson said. “It’s different from tapering a drug; this is something that you have to plan for. Tapering video games is difficult to do. If the kid plays longer than they’re supposed to, what do you do then? You may have a fight to discontinue the video game. That’s one of the practical problems.”
Dr. Atkinson reported having no financial disclosures.
SOURCE: Atkinson DL. AAAP 2017.
SAN DIEGO – As a medical student, David L. Atkinson, MD, learned about a group of five adult men who played EverQuest, which bills itself as a 3D online world that “offers endless excitement, adventure, battle, and discovery.” They shared an apartment in Austin, Tex., and rotated which one would hold a full-time job while the other four spent their waking hours playing EverQuest.
“It was a little concerning,” recalled Dr. Atkinson, now a psychiatrist and the medical director of the teen recovery program at Children’s Health, Dallas. “EverQuest had a button in the game where you could order a pizza without interrupting your game play. Pathological video game use can be incredibly life-dominating.”
Many terms are used for pathological video game use, including problematic video game use, gaming disorder, and Internet gaming disorder, which is the term used in section III of DSM-5. Whether chronic video game use is a societal problem or an individual problem “is a very big question,” Dr. Atkinson said. “When we look at some of the prevalence data from Monitoring the Future, we have seen reductions in all kinds of substance use. We have seen reductions in teenage motor vehicle accidents and in teen pregnancy. If kids are playing video games and they’re all getting out of shape, that’s a cultural challenge. A clinician, though, may advocate against it as part of good health care.
“For instance, underage drinking in some American subcultures is normative. It doesn’t mean it’s a good idea.”
Most youth do not develop addictive behavior from playing games like EverQuest. “Substance use and gaming are different,” Dr. Atkinson said. “The amount of time spent at the expense of other things is one of the primary harms of video gaming, but financial concerns are not irrelevant. The new Star Wars Battlefront game would cost $2,100 if someone were to buy all of the available extras for the video game. Otherwise, it would take several hundred hours of game play to achieve all of these unlocked features.” While video games do not induce supraphysiologic dopamine release in the way drugs like cocaine do, the addictive potential is measured by an equation of reward versus effort. Obtaining a video game is not dependent upon social interactions, unlike drug use in states where the drug in question is illegal. In fact, the fewer social connections, the greater the risk of developing a video game use disorder.
“The perception of harm of video game addiction is very low, and parents do not consider the potential for developing an addiction before they buy a computer, handheld device, or video game console,” he said. “It is viewed as something that has to be limited ... not as something that is impossible to limit.” However, when parents begin to detect problems, they often find themselves unable to control their children’s or teens’ use of gaming, according to Dr. Atkinson.
In the DSM-5, Internet gaming disorder is defined as being preoccupied with games and withdrawn when not playing them, including irritability, anxiety, and sadness. Tolerance manifests as needing to spend more time playing the game. Typically, gamers cannot reduce their use despite effort, and there is a loss of interest in other activities and hobbies, Dr. Atkinson said. They may continue to engage in overuse of games despite knowing it’s a problem; they may lie about usage, may use games to escape anxiety or guilt, and may have lost or risked lose or risk relationships or career opportunities because of games.
“Not all gamers will do all of these things,” he emphasized. “For example, some gamers have disordered use and lose interest in other things, but don’t lie about it.” DSM-5 criteria also note that the video gaming itself must cause clinically significant impairment and must not be a manifestation of another disorder.
Tools aimed at helping in the diagnosis include the Problem Video Game Playing Questionnaire, the Internet Gaming Disorder Scale, the Internet Gaming Disorder Scale–Short-Form, the Problematic Online Gaming Questionnaire, the Game Addiction Scale, and the Electronic Gaming Motives Questionnaire, which measures enhancement, coping, social, and self-gratification motives.
According to Dr. Atkinson, 90% of children in Japan, Korea, North America, and Europe play video games. However, the prevalence of Internet gaming disorder is estimated to be 1% in the United States, 1.14% in Germany, and 5.9% in South Korea. Males have higher rates of pathological video game use, while afflicted females tend to have more problems. Pathological gaming use is associated with high levels of previous truancy and few leisure activities. It’s also associated with depression, poor impulse control, narcissistic traits, high anxiety, poor social competence, and less religiosity.
“The overlap with depression is very interesting,” Dr. Atkinson said. “ When they get rejected in a peer group or for a job, they tend to take it harder than people who don’t game. The gaming world is a place where you can be safe from rejection. If your credit card goes through, you’re allowed in.”
Anhedonia is another factor within the clinical syndrome of depression that is associated with video game use. A nationwide community sample of individuals in Korea showed that gaming and depression have their overlap most strongly with the “escape from negative emotions” model (J Nerv Ment Dis. 2017;205[7]:568-73). Other associated problems include greater obesity; metabolic indicators, such as high triglycerides and cholesterol; and sleep deprivation. Chronic gamers also tend to have less social support, less health promotion, and heightened social phobia. “When you’re gaming all the time, you’re going to have less opportunity to engage in an exposure paradigm to help you get over your social phobia,” Dr. Atkinson said. “Problem gamers are also more likely to have pathological use of pornography, poor impulse control, and ADHD symptoms.”
Studies of biobehavioral characteristics of those with pathological video game use suggest that there is a decreased dopamine striatal response (Neurosci Biobehav Rev. 2017 Apr;75:314-30). They also suggest decreased functional connectivity across areas of the brain, including decreased resting-state functional connectivity between ventral tegmental area and the nucleus accumbens, and lower tonic dopamine firing.
Parental management training can be successful at setting gaming limits in children under 12 years of age, he said. Pathological video game use is associated with physiologic stress in the family problem-solving task. One study of a brief 3-week family therapy intervention as measured by functional MRI showed that improvement in perceived family cohesion was associated with an increase in the activity of the caudate nucleus in response to the gamer’s viewing images of family cohesion and was inversely correlated with changes in online game playing time (Psychiatry Res. 2012 May 31;202[2]:126-31). “Bringing the family together may give them something to do besides gaming,” Dr. Atkinson said. “That can help them put games in a more balanced perspective.”
The largest evidence base supports cognitive-behavioral therapy for Internet gaming disorder, but there is insufficient evidence to make a clear statement of benefit (Clin Psychol Rev. 2017 Jun;54:123-33). Gaming-related cognitions accounted for a large portion of the variance in treatment response.
“Does the gaming cause the thoughts? Or do the thoughts cause the gaming?” Dr. Atkinson asked. “The cognitive model of CBT would tell you there’s a bidirectional relationship.”
As for medications, bupropion has been shown to reduce online gaming in depressed individuals, and escitalopram also may be efficacious. One comparative analysis showed that there were greater effects from using bupropion than for using escitalopram (Clin Psychopharmacol Neurosci. 2017 Nov 30;15[4]:361-8). Methylphenidate also has been shown to reduce online gaming (Compr Psychiatry. 2009 May-Jun;50[3]:251-6).
Parents who take video games away from their children often are met with a burst of aggression. “There’s an attempt to reestablish dominance in the situation, to obtain the old reinforcer or to reestablish control,” Dr. Atkinson said. “It’s different from tapering a drug; this is something that you have to plan for. Tapering video games is difficult to do. If the kid plays longer than they’re supposed to, what do you do then? You may have a fight to discontinue the video game. That’s one of the practical problems.”
Dr. Atkinson reported having no financial disclosures.
SOURCE: Atkinson DL. AAAP 2017.
REPORTING FROM AAAP
When cloth diapers cause diaper dermatitis, think calcineurin inhibitors
, a reemerging complication of diaper dermatitis associated with use of cloth reusable diapers, wrote Rita Ramos Pinheiro, MD, of Hospital Santo António dos Capuchos, Lisbon, and her associates.
An otherwise healthy 18-month-old girl was referred to the dermatology clinic with a 9-month history of severe relapsing diaper dermatitis, which responded to topical clotrimazole and zinc oxide cream. Nondisposable cloth diapers were used. She returned with a rash unresponsive to barrier creams, topical antibiotics and antifungals, and a variety of topical corticosteroids.
Clinically, a diagnosis of granuloma gluteale infantum was suspected; this was confirmed by a skin biopsy of one of the nodules.
The parents declined to stop using cloth diapers, so general measures to alleviate diaper dermatitis were tried, including frequent diaper-free periods. All previous topical treatments were stopped. A 0.1% pimecrolimus cream applied daily for 1 month was well tolerated, and a more potent 0.03% tacrolimus cream then was applied; both medications are topical calcineurin inhibitors.
At 4 weeks, there was complete regression of the ulcerated lesions, with later thinning of the lesions. At the last examination, there remained only slightly hypopigmented residual patches.
The same general measures were continued, including use of barrier creams. The patient had a relapse at her 9-month follow-up, with three nodules occurring on the gluteal region; these resolved with application of topical tacrolimus cream for 1 week.
Although reusable cloth diapers are considered better for the environment and cheaper than disposable diapers, “purportedly” they are less absorbent than disposable diapers, the investigators said.
Characteristics of the clinical diagnosis of granuloma gluteale infantum are “red-purple to red-brown, round to oval, deep, firm nodules with central ulceration,” with a “classic distribution over the convexities of the gluteal region, sparing the inguinal folds,” Dr. Pinheiro and her associates observed. The case study is the first reporting the use of topical calcineurin inhibitors for treating granuloma gluteale infantum, the researchers asserted.
Read more at Pediatrics (2017 Jan 3. doi: 10.1542/peds.2016-2064).
, a reemerging complication of diaper dermatitis associated with use of cloth reusable diapers, wrote Rita Ramos Pinheiro, MD, of Hospital Santo António dos Capuchos, Lisbon, and her associates.
An otherwise healthy 18-month-old girl was referred to the dermatology clinic with a 9-month history of severe relapsing diaper dermatitis, which responded to topical clotrimazole and zinc oxide cream. Nondisposable cloth diapers were used. She returned with a rash unresponsive to barrier creams, topical antibiotics and antifungals, and a variety of topical corticosteroids.
Clinically, a diagnosis of granuloma gluteale infantum was suspected; this was confirmed by a skin biopsy of one of the nodules.
The parents declined to stop using cloth diapers, so general measures to alleviate diaper dermatitis were tried, including frequent diaper-free periods. All previous topical treatments were stopped. A 0.1% pimecrolimus cream applied daily for 1 month was well tolerated, and a more potent 0.03% tacrolimus cream then was applied; both medications are topical calcineurin inhibitors.
At 4 weeks, there was complete regression of the ulcerated lesions, with later thinning of the lesions. At the last examination, there remained only slightly hypopigmented residual patches.
The same general measures were continued, including use of barrier creams. The patient had a relapse at her 9-month follow-up, with three nodules occurring on the gluteal region; these resolved with application of topical tacrolimus cream for 1 week.
Although reusable cloth diapers are considered better for the environment and cheaper than disposable diapers, “purportedly” they are less absorbent than disposable diapers, the investigators said.
Characteristics of the clinical diagnosis of granuloma gluteale infantum are “red-purple to red-brown, round to oval, deep, firm nodules with central ulceration,” with a “classic distribution over the convexities of the gluteal region, sparing the inguinal folds,” Dr. Pinheiro and her associates observed. The case study is the first reporting the use of topical calcineurin inhibitors for treating granuloma gluteale infantum, the researchers asserted.
Read more at Pediatrics (2017 Jan 3. doi: 10.1542/peds.2016-2064).
, a reemerging complication of diaper dermatitis associated with use of cloth reusable diapers, wrote Rita Ramos Pinheiro, MD, of Hospital Santo António dos Capuchos, Lisbon, and her associates.
An otherwise healthy 18-month-old girl was referred to the dermatology clinic with a 9-month history of severe relapsing diaper dermatitis, which responded to topical clotrimazole and zinc oxide cream. Nondisposable cloth diapers were used. She returned with a rash unresponsive to barrier creams, topical antibiotics and antifungals, and a variety of topical corticosteroids.
Clinically, a diagnosis of granuloma gluteale infantum was suspected; this was confirmed by a skin biopsy of one of the nodules.
The parents declined to stop using cloth diapers, so general measures to alleviate diaper dermatitis were tried, including frequent diaper-free periods. All previous topical treatments were stopped. A 0.1% pimecrolimus cream applied daily for 1 month was well tolerated, and a more potent 0.03% tacrolimus cream then was applied; both medications are topical calcineurin inhibitors.
At 4 weeks, there was complete regression of the ulcerated lesions, with later thinning of the lesions. At the last examination, there remained only slightly hypopigmented residual patches.
The same general measures were continued, including use of barrier creams. The patient had a relapse at her 9-month follow-up, with three nodules occurring on the gluteal region; these resolved with application of topical tacrolimus cream for 1 week.
Although reusable cloth diapers are considered better for the environment and cheaper than disposable diapers, “purportedly” they are less absorbent than disposable diapers, the investigators said.
Characteristics of the clinical diagnosis of granuloma gluteale infantum are “red-purple to red-brown, round to oval, deep, firm nodules with central ulceration,” with a “classic distribution over the convexities of the gluteal region, sparing the inguinal folds,” Dr. Pinheiro and her associates observed. The case study is the first reporting the use of topical calcineurin inhibitors for treating granuloma gluteale infantum, the researchers asserted.
Read more at Pediatrics (2017 Jan 3. doi: 10.1542/peds.2016-2064).
FROM PEDIATRICS
Cases link vitiligoid lichen sclerosus and darker skin
, said Margaret H. Dennin, of the University of Chicago, and her associates.
Vitiligoid lichen sclerosus is a superficial variant of lichen sclerosus (LS), in which the lesion clinically appears to be vitiligo, but histologically is consistent with LS.
Seven dark-skinned girls aged 3-9 years had symptomatic (pruritus, pain, bleeding, constipation) depigmented patches of the vulvar or perianal region; three had purpuric lesions. None of the patients had atrophy or scarring, and they had no depigmentation anywhere else on their bodies. Follow-up was an average 2 years (range 3 months to 4 years).
Treatment with high-potency topical steroids, calcineurin inhibitors, or both resulted in improvement or resolution of their symptoms in all cases, but there was mild or no improvement in the depigmentation. Biopsies were not performed because of the patients’ young age and the location of the lesions, the investigators said.
The term vitiligoid lichen sclerosus was first coined in 1961 by Borda et al. when depigmented patches, as seen in both conditions, constituted the clinical appearance, but lacked the inflammation, atrophy, and sclerosis of typical LS. Histologically, these lesions were like LS, “based on the presence of a thin band of papillary dermal sclerosis,” Ms. Dennin and her associates said. Borda et al. suggested that vitiligoid lichen sclerosus might be limited to dark-skinned people, and recent reports support this. Alternatively, it may be that the depigmentation simply is more obvious on dark-skinned people, and asymptomatic cases go unnoticed on lighter-skinned people, the investigators surmised.
Both vitiligo and LS are autoimmune cutaneous disorders, and they both often affect the anogenital region. The conditions “may be linked through a common autoimmune response from exposed intracellular or altered cell surface antigens on damaged melanocytes,” the investigators said. “Histologic evidence demonstrates that development of vitiligo involves a preceding lichenoid inflammatory reaction that may trigger an autoimmune reaction to melanocytes, decreasing their number. Evolving vitiligo with a lichenoid reaction may result in epitope spreading and the development of LS.”
The study is limited by its retrospective nature, small sample size, and lack of biopsies, the researchers noted. Larger studies are needed to look at the overlap of the conditions, and “understand the true prevalence of vitiligoid lichen sclerosus,” Ms. Dennin and her associates said.
Read more in Pediatric Dermatology (2018. doi: 10.1111/pde.13399).
, said Margaret H. Dennin, of the University of Chicago, and her associates.
Vitiligoid lichen sclerosus is a superficial variant of lichen sclerosus (LS), in which the lesion clinically appears to be vitiligo, but histologically is consistent with LS.
Seven dark-skinned girls aged 3-9 years had symptomatic (pruritus, pain, bleeding, constipation) depigmented patches of the vulvar or perianal region; three had purpuric lesions. None of the patients had atrophy or scarring, and they had no depigmentation anywhere else on their bodies. Follow-up was an average 2 years (range 3 months to 4 years).
Treatment with high-potency topical steroids, calcineurin inhibitors, or both resulted in improvement or resolution of their symptoms in all cases, but there was mild or no improvement in the depigmentation. Biopsies were not performed because of the patients’ young age and the location of the lesions, the investigators said.
The term vitiligoid lichen sclerosus was first coined in 1961 by Borda et al. when depigmented patches, as seen in both conditions, constituted the clinical appearance, but lacked the inflammation, atrophy, and sclerosis of typical LS. Histologically, these lesions were like LS, “based on the presence of a thin band of papillary dermal sclerosis,” Ms. Dennin and her associates said. Borda et al. suggested that vitiligoid lichen sclerosus might be limited to dark-skinned people, and recent reports support this. Alternatively, it may be that the depigmentation simply is more obvious on dark-skinned people, and asymptomatic cases go unnoticed on lighter-skinned people, the investigators surmised.
Both vitiligo and LS are autoimmune cutaneous disorders, and they both often affect the anogenital region. The conditions “may be linked through a common autoimmune response from exposed intracellular or altered cell surface antigens on damaged melanocytes,” the investigators said. “Histologic evidence demonstrates that development of vitiligo involves a preceding lichenoid inflammatory reaction that may trigger an autoimmune reaction to melanocytes, decreasing their number. Evolving vitiligo with a lichenoid reaction may result in epitope spreading and the development of LS.”
The study is limited by its retrospective nature, small sample size, and lack of biopsies, the researchers noted. Larger studies are needed to look at the overlap of the conditions, and “understand the true prevalence of vitiligoid lichen sclerosus,” Ms. Dennin and her associates said.
Read more in Pediatric Dermatology (2018. doi: 10.1111/pde.13399).
, said Margaret H. Dennin, of the University of Chicago, and her associates.
Vitiligoid lichen sclerosus is a superficial variant of lichen sclerosus (LS), in which the lesion clinically appears to be vitiligo, but histologically is consistent with LS.
Seven dark-skinned girls aged 3-9 years had symptomatic (pruritus, pain, bleeding, constipation) depigmented patches of the vulvar or perianal region; three had purpuric lesions. None of the patients had atrophy or scarring, and they had no depigmentation anywhere else on their bodies. Follow-up was an average 2 years (range 3 months to 4 years).
Treatment with high-potency topical steroids, calcineurin inhibitors, or both resulted in improvement or resolution of their symptoms in all cases, but there was mild or no improvement in the depigmentation. Biopsies were not performed because of the patients’ young age and the location of the lesions, the investigators said.
The term vitiligoid lichen sclerosus was first coined in 1961 by Borda et al. when depigmented patches, as seen in both conditions, constituted the clinical appearance, but lacked the inflammation, atrophy, and sclerosis of typical LS. Histologically, these lesions were like LS, “based on the presence of a thin band of papillary dermal sclerosis,” Ms. Dennin and her associates said. Borda et al. suggested that vitiligoid lichen sclerosus might be limited to dark-skinned people, and recent reports support this. Alternatively, it may be that the depigmentation simply is more obvious on dark-skinned people, and asymptomatic cases go unnoticed on lighter-skinned people, the investigators surmised.
Both vitiligo and LS are autoimmune cutaneous disorders, and they both often affect the anogenital region. The conditions “may be linked through a common autoimmune response from exposed intracellular or altered cell surface antigens on damaged melanocytes,” the investigators said. “Histologic evidence demonstrates that development of vitiligo involves a preceding lichenoid inflammatory reaction that may trigger an autoimmune reaction to melanocytes, decreasing their number. Evolving vitiligo with a lichenoid reaction may result in epitope spreading and the development of LS.”
The study is limited by its retrospective nature, small sample size, and lack of biopsies, the researchers noted. Larger studies are needed to look at the overlap of the conditions, and “understand the true prevalence of vitiligoid lichen sclerosus,” Ms. Dennin and her associates said.
Read more in Pediatric Dermatology (2018. doi: 10.1111/pde.13399).
FROM PEDIATRIC DERMATOLOGY
U.S. influenza activity widespread to start 2018
As far as the influenza virus is concerned, the new year started in the same way as the old one ended: with almost half of the states at the highest level of flu activity, according to the Centers for Disease Control and Prevention.
For the week ending Jan. 6, 2018, there were 23 states – including California, Illinois, and Texas – at level 10 on the CDC’s 1-10 scale for influenza-like illness (ILI) activity, which was up from 22 for the last full week of 2017. Joining the 23 states in the “high” range were New Jersey and Ohio at level 9 and Colorado at level 8, the CDC’s influenza division reported Jan. 12.
Seven flu-related pediatric deaths were reported during the week ending Jan. 6, although one occurred during the week ending Dec. 16 and two were during the week ending Dec. 23. There have been a total of 20 pediatric deaths related to influenza so far for the 2017-2018 season, the CDC said. In 2016-2017, there were 110 pediatric deaths from the flu.
As far as the influenza virus is concerned, the new year started in the same way as the old one ended: with almost half of the states at the highest level of flu activity, according to the Centers for Disease Control and Prevention.
For the week ending Jan. 6, 2018, there were 23 states – including California, Illinois, and Texas – at level 10 on the CDC’s 1-10 scale for influenza-like illness (ILI) activity, which was up from 22 for the last full week of 2017. Joining the 23 states in the “high” range were New Jersey and Ohio at level 9 and Colorado at level 8, the CDC’s influenza division reported Jan. 12.
Seven flu-related pediatric deaths were reported during the week ending Jan. 6, although one occurred during the week ending Dec. 16 and two were during the week ending Dec. 23. There have been a total of 20 pediatric deaths related to influenza so far for the 2017-2018 season, the CDC said. In 2016-2017, there were 110 pediatric deaths from the flu.
As far as the influenza virus is concerned, the new year started in the same way as the old one ended: with almost half of the states at the highest level of flu activity, according to the Centers for Disease Control and Prevention.
For the week ending Jan. 6, 2018, there were 23 states – including California, Illinois, and Texas – at level 10 on the CDC’s 1-10 scale for influenza-like illness (ILI) activity, which was up from 22 for the last full week of 2017. Joining the 23 states in the “high” range were New Jersey and Ohio at level 9 and Colorado at level 8, the CDC’s influenza division reported Jan. 12.
Seven flu-related pediatric deaths were reported during the week ending Jan. 6, although one occurred during the week ending Dec. 16 and two were during the week ending Dec. 23. There have been a total of 20 pediatric deaths related to influenza so far for the 2017-2018 season, the CDC said. In 2016-2017, there were 110 pediatric deaths from the flu.
Young e-cigarette users graduating to the real thing
Children who use noncigarette forms of tobacco are significantly more likely to try cigarettes in the future, according to survey data from over 10,000 young people aged 12-17 years.
An initial survey (wave 1) was conducted as part of the nationally representative Population Assessment of Tobacco and Health (PATH) study, with a follow-up (wave 2) administered to participants a year later. The analysis by Shannon L. Watkins, PhD, of the University of California, San Francisco, and her associates was based on data for 10,384 respondents who reported never smoking a cigarette in wave 1 and whose later cigarette use, which occurred in less than 5% overall, was reported in wave 2.
Those who used multiple noncigarette products were more likely than users of a single product to initiate cigarette use by wave 2. With never use of any tobacco as the reference, one model used by the investigators put the odds ratios of cigarette ever use at 4.98 for e-cigarettes only, 3.57 for combustibles only, and 8.57 for use of multiple products.
This study was supported by grants from the National Cancer Institute, Food and Drug Administration Center for Tobacco Products, National Institute on Drug Abuse, and National Center for Advancing Translational Sciences. No conflicts of interest were reported.
SOURCE: Watkins S et al. JAMA Pediatr. 2018 Jan 2. doi: 10.1001/jamapediatrics.2017.4173.
Children who use noncigarette forms of tobacco are significantly more likely to try cigarettes in the future, according to survey data from over 10,000 young people aged 12-17 years.
An initial survey (wave 1) was conducted as part of the nationally representative Population Assessment of Tobacco and Health (PATH) study, with a follow-up (wave 2) administered to participants a year later. The analysis by Shannon L. Watkins, PhD, of the University of California, San Francisco, and her associates was based on data for 10,384 respondents who reported never smoking a cigarette in wave 1 and whose later cigarette use, which occurred in less than 5% overall, was reported in wave 2.
Those who used multiple noncigarette products were more likely than users of a single product to initiate cigarette use by wave 2. With never use of any tobacco as the reference, one model used by the investigators put the odds ratios of cigarette ever use at 4.98 for e-cigarettes only, 3.57 for combustibles only, and 8.57 for use of multiple products.
This study was supported by grants from the National Cancer Institute, Food and Drug Administration Center for Tobacco Products, National Institute on Drug Abuse, and National Center for Advancing Translational Sciences. No conflicts of interest were reported.
SOURCE: Watkins S et al. JAMA Pediatr. 2018 Jan 2. doi: 10.1001/jamapediatrics.2017.4173.
Children who use noncigarette forms of tobacco are significantly more likely to try cigarettes in the future, according to survey data from over 10,000 young people aged 12-17 years.
An initial survey (wave 1) was conducted as part of the nationally representative Population Assessment of Tobacco and Health (PATH) study, with a follow-up (wave 2) administered to participants a year later. The analysis by Shannon L. Watkins, PhD, of the University of California, San Francisco, and her associates was based on data for 10,384 respondents who reported never smoking a cigarette in wave 1 and whose later cigarette use, which occurred in less than 5% overall, was reported in wave 2.
Those who used multiple noncigarette products were more likely than users of a single product to initiate cigarette use by wave 2. With never use of any tobacco as the reference, one model used by the investigators put the odds ratios of cigarette ever use at 4.98 for e-cigarettes only, 3.57 for combustibles only, and 8.57 for use of multiple products.
This study was supported by grants from the National Cancer Institute, Food and Drug Administration Center for Tobacco Products, National Institute on Drug Abuse, and National Center for Advancing Translational Sciences. No conflicts of interest were reported.
SOURCE: Watkins S et al. JAMA Pediatr. 2018 Jan 2. doi: 10.1001/jamapediatrics.2017.4173.
FROM JAMA PEDIATRICS
Behavioral issues, anorexia may presage celiac disease
The clinical challenges of celiac disease go beyond identifying the condition and helping families adjust to a child’s gluten-free diet. Behavioral problems and/or an eating disorder may predate celiac disease, according to Alex R. Kemper, MD, MPH, division chief of ambulatory pediatrics at Nationwide Children’s Hospital, Columbus, Ohio, and deputy editor of Pediatrics.
“We are learning more and more about celiac disease. The presentation and implication of celiac disease can involve more than the gastrointestinal tract,” Dr. Kemper noted. “Figuring out who to screen for celiac disease and how best to do so is complex, and we are always learning more about the best way to provide care after celiac disease is diagnosed.”
Impact of undiagnosed celiac disease on behavior
At the 2017 annual meeting of the American Academy of Pediatrics and, in a later interview, Dr. Kemper discussed a study that explored how behavior and celiac disease might be interrelated, particularly among children whose families don’t yet know their child has the condition.
“It’s challenging to assess the psychological impact of celiac disease autoimmunity when families aren’t aware a child has it, because prospective studies are difficult to do and recall bias can distort findings,” he noted.
Smith et al. used data from a prospective international study, The Environment Determinants of Diabetes in the Young (TEDDY), designed to learn about factors associated with type 1 diabetes and celiac disease over a 15-year follow-up period (Pediatrics. 2017 Mar. doi: 10.1542/peds.2016-2848).
TEDDY tracked 8,676 infants deemed at high risk for celiac autoimmunity based on their human leukocyte antigen (HLA) antigen status at birth. The investigators regularly measured celiac disease autoimmunity based on tissue transglutaminase antibodies (tTGA), beginning at age 2 years. They assessed the children’s behavior at ages 3.5 years and 4.5 years using the Achenbach System of Empirically Based Assessment. If a child was found to have celiac disease, the researchers revisited the earlier behavior scores reported by their mothers before their children’s status were known.
When the children were 3.5 years old, 66 had celiac disease that their mothers were not yet aware of and 440 children had diagnosed celiac disease. The 66 mothers unaware of their child’s condition reported more anxiety, depression, aggression, and sleep problems in their children than did the 440 mothers who knew their child’s diagnosis or the 3,651 mothers of children without celiac disease. The differences were subclinical but statistically significant.
“It is important to recognize that the magnitude of the psychological problems in the 3.5 year olds was small,” Dr. Kemper said in an interview. “Parents might not recognize these symptoms.”
When the researchers looked at child behavior reports only among the mothers who knew their children had celiac disease, no differences existed regardless of the children’s tTGA levels or whether they were following a gluten-free diet. Then, when the children were 4.5 years old and all mothers were aware of their child’s status, no significant differences in mothers’ reporting of child behavior existed across any of the groups.
“Perhaps the knowledge of the child’s celiac disease autoimmunity increases a parent’s sensitivity to physical discomforts of their child while providing an alternative explanation for any psychological symptoms the child exhibits,” the researchers offered.
“Pediatricians should be aware of this association and consider testing young children with a family history of celiac disease if there are concerns,” Dr. Kemper said in an interview. “Because the magnitude of change was subclinical, this study does not suggest the need for more extensive screening of all children.”
Link between celiac disease and anorexia nervosa
The eating disorders study Dr. Kemper discussed examined possible associations between celiac disease and anorexia nervosa (Pediatrics. 2017. doi: 10.1542/peds.2016-4367). Researchers compared 17,959 Swedish females diagnosed with celiac disease between 1969 and 2008, at a median 28 years old, to 89,379 controls matched by sex and age.
Anorexia occurred more often among those with celiac disease than those without: a rate of 27 girls per 100,000 with celiac disease developed anorexia per year, compared with 18 of 100,000 without celiac disease, for a hazard ratio for an anorexia nervosa diagnosis of 1.46 (95% confidence interval, 1.08-1.98). In addition, girls whose celiac disease had not yet been identified had more than double the odds of developing anorexia before diagnosis than did those without celiac disease (odds ratio, 2.13).
Females with celiac disease therefore were more likely to have anorexia both before and after their celiac diagnosis, although the authors noted that surveillance bias may have made it more likely for either of the patients’ conditions to be identified after the first was. Another possible explanation is shared genetic risk factors, the authors wrote.
Dr. Kemper also offered possible reasons, including one related to the child behavior study.
“It could be that girls with celiac disease might develop anorexia because of the need to focus on their diet,” he said in an interview. “Celiac disease has been associated with psychological problems, and so that could contribute.”
Until further research can shed light on the reasons for the associations, physicians simply should be aware of the study’s clinical implications.
“Pediatricians should be aware of the bidirectional association between celiac disease and anorexia nervosa in teens and young adult women, and be prepared to evaluate for celiac disease or treat anorexia,” Dr. Kemper said.
He noted the need for more research to learn “what pediatricians can do to help to either prevent these problems from developing in the first place, or identify and treat celiac disease or anorexia nervosa early to prevent long-term complications.”
Dr. Kemper reported having no relevant financial disclosures and no external funding. Ketil Stordal, MD, PhD, of the anorexia study received funding from the OAK foundation in Switzerland, and Cynthia M. Bulik, PhD, from the same study received funding from the Swedish Research Council, and has consulted for and received a grant from Shire. The remaining authors of the anorexia study had no relevant financial disclosures. The behavioral study was funded by the National Institutes of Health, the Juvenile Diabetes Research Foundation and the Centers for Disease Control and Prevention. The authors from the behavioral study had no relevant financial disclosures.
The clinical challenges of celiac disease go beyond identifying the condition and helping families adjust to a child’s gluten-free diet. Behavioral problems and/or an eating disorder may predate celiac disease, according to Alex R. Kemper, MD, MPH, division chief of ambulatory pediatrics at Nationwide Children’s Hospital, Columbus, Ohio, and deputy editor of Pediatrics.
“We are learning more and more about celiac disease. The presentation and implication of celiac disease can involve more than the gastrointestinal tract,” Dr. Kemper noted. “Figuring out who to screen for celiac disease and how best to do so is complex, and we are always learning more about the best way to provide care after celiac disease is diagnosed.”
Impact of undiagnosed celiac disease on behavior
At the 2017 annual meeting of the American Academy of Pediatrics and, in a later interview, Dr. Kemper discussed a study that explored how behavior and celiac disease might be interrelated, particularly among children whose families don’t yet know their child has the condition.
“It’s challenging to assess the psychological impact of celiac disease autoimmunity when families aren’t aware a child has it, because prospective studies are difficult to do and recall bias can distort findings,” he noted.
Smith et al. used data from a prospective international study, The Environment Determinants of Diabetes in the Young (TEDDY), designed to learn about factors associated with type 1 diabetes and celiac disease over a 15-year follow-up period (Pediatrics. 2017 Mar. doi: 10.1542/peds.2016-2848).
TEDDY tracked 8,676 infants deemed at high risk for celiac autoimmunity based on their human leukocyte antigen (HLA) antigen status at birth. The investigators regularly measured celiac disease autoimmunity based on tissue transglutaminase antibodies (tTGA), beginning at age 2 years. They assessed the children’s behavior at ages 3.5 years and 4.5 years using the Achenbach System of Empirically Based Assessment. If a child was found to have celiac disease, the researchers revisited the earlier behavior scores reported by their mothers before their children’s status were known.
When the children were 3.5 years old, 66 had celiac disease that their mothers were not yet aware of and 440 children had diagnosed celiac disease. The 66 mothers unaware of their child’s condition reported more anxiety, depression, aggression, and sleep problems in their children than did the 440 mothers who knew their child’s diagnosis or the 3,651 mothers of children without celiac disease. The differences were subclinical but statistically significant.
“It is important to recognize that the magnitude of the psychological problems in the 3.5 year olds was small,” Dr. Kemper said in an interview. “Parents might not recognize these symptoms.”
When the researchers looked at child behavior reports only among the mothers who knew their children had celiac disease, no differences existed regardless of the children’s tTGA levels or whether they were following a gluten-free diet. Then, when the children were 4.5 years old and all mothers were aware of their child’s status, no significant differences in mothers’ reporting of child behavior existed across any of the groups.
“Perhaps the knowledge of the child’s celiac disease autoimmunity increases a parent’s sensitivity to physical discomforts of their child while providing an alternative explanation for any psychological symptoms the child exhibits,” the researchers offered.
“Pediatricians should be aware of this association and consider testing young children with a family history of celiac disease if there are concerns,” Dr. Kemper said in an interview. “Because the magnitude of change was subclinical, this study does not suggest the need for more extensive screening of all children.”
Link between celiac disease and anorexia nervosa
The eating disorders study Dr. Kemper discussed examined possible associations between celiac disease and anorexia nervosa (Pediatrics. 2017. doi: 10.1542/peds.2016-4367). Researchers compared 17,959 Swedish females diagnosed with celiac disease between 1969 and 2008, at a median 28 years old, to 89,379 controls matched by sex and age.
Anorexia occurred more often among those with celiac disease than those without: a rate of 27 girls per 100,000 with celiac disease developed anorexia per year, compared with 18 of 100,000 without celiac disease, for a hazard ratio for an anorexia nervosa diagnosis of 1.46 (95% confidence interval, 1.08-1.98). In addition, girls whose celiac disease had not yet been identified had more than double the odds of developing anorexia before diagnosis than did those without celiac disease (odds ratio, 2.13).
Females with celiac disease therefore were more likely to have anorexia both before and after their celiac diagnosis, although the authors noted that surveillance bias may have made it more likely for either of the patients’ conditions to be identified after the first was. Another possible explanation is shared genetic risk factors, the authors wrote.
Dr. Kemper also offered possible reasons, including one related to the child behavior study.
“It could be that girls with celiac disease might develop anorexia because of the need to focus on their diet,” he said in an interview. “Celiac disease has been associated with psychological problems, and so that could contribute.”
Until further research can shed light on the reasons for the associations, physicians simply should be aware of the study’s clinical implications.
“Pediatricians should be aware of the bidirectional association between celiac disease and anorexia nervosa in teens and young adult women, and be prepared to evaluate for celiac disease or treat anorexia,” Dr. Kemper said.
He noted the need for more research to learn “what pediatricians can do to help to either prevent these problems from developing in the first place, or identify and treat celiac disease or anorexia nervosa early to prevent long-term complications.”
Dr. Kemper reported having no relevant financial disclosures and no external funding. Ketil Stordal, MD, PhD, of the anorexia study received funding from the OAK foundation in Switzerland, and Cynthia M. Bulik, PhD, from the same study received funding from the Swedish Research Council, and has consulted for and received a grant from Shire. The remaining authors of the anorexia study had no relevant financial disclosures. The behavioral study was funded by the National Institutes of Health, the Juvenile Diabetes Research Foundation and the Centers for Disease Control and Prevention. The authors from the behavioral study had no relevant financial disclosures.
The clinical challenges of celiac disease go beyond identifying the condition and helping families adjust to a child’s gluten-free diet. Behavioral problems and/or an eating disorder may predate celiac disease, according to Alex R. Kemper, MD, MPH, division chief of ambulatory pediatrics at Nationwide Children’s Hospital, Columbus, Ohio, and deputy editor of Pediatrics.
“We are learning more and more about celiac disease. The presentation and implication of celiac disease can involve more than the gastrointestinal tract,” Dr. Kemper noted. “Figuring out who to screen for celiac disease and how best to do so is complex, and we are always learning more about the best way to provide care after celiac disease is diagnosed.”
Impact of undiagnosed celiac disease on behavior
At the 2017 annual meeting of the American Academy of Pediatrics and, in a later interview, Dr. Kemper discussed a study that explored how behavior and celiac disease might be interrelated, particularly among children whose families don’t yet know their child has the condition.
“It’s challenging to assess the psychological impact of celiac disease autoimmunity when families aren’t aware a child has it, because prospective studies are difficult to do and recall bias can distort findings,” he noted.
Smith et al. used data from a prospective international study, The Environment Determinants of Diabetes in the Young (TEDDY), designed to learn about factors associated with type 1 diabetes and celiac disease over a 15-year follow-up period (Pediatrics. 2017 Mar. doi: 10.1542/peds.2016-2848).
TEDDY tracked 8,676 infants deemed at high risk for celiac autoimmunity based on their human leukocyte antigen (HLA) antigen status at birth. The investigators regularly measured celiac disease autoimmunity based on tissue transglutaminase antibodies (tTGA), beginning at age 2 years. They assessed the children’s behavior at ages 3.5 years and 4.5 years using the Achenbach System of Empirically Based Assessment. If a child was found to have celiac disease, the researchers revisited the earlier behavior scores reported by their mothers before their children’s status were known.
When the children were 3.5 years old, 66 had celiac disease that their mothers were not yet aware of and 440 children had diagnosed celiac disease. The 66 mothers unaware of their child’s condition reported more anxiety, depression, aggression, and sleep problems in their children than did the 440 mothers who knew their child’s diagnosis or the 3,651 mothers of children without celiac disease. The differences were subclinical but statistically significant.
“It is important to recognize that the magnitude of the psychological problems in the 3.5 year olds was small,” Dr. Kemper said in an interview. “Parents might not recognize these symptoms.”
When the researchers looked at child behavior reports only among the mothers who knew their children had celiac disease, no differences existed regardless of the children’s tTGA levels or whether they were following a gluten-free diet. Then, when the children were 4.5 years old and all mothers were aware of their child’s status, no significant differences in mothers’ reporting of child behavior existed across any of the groups.
“Perhaps the knowledge of the child’s celiac disease autoimmunity increases a parent’s sensitivity to physical discomforts of their child while providing an alternative explanation for any psychological symptoms the child exhibits,” the researchers offered.
“Pediatricians should be aware of this association and consider testing young children with a family history of celiac disease if there are concerns,” Dr. Kemper said in an interview. “Because the magnitude of change was subclinical, this study does not suggest the need for more extensive screening of all children.”
Link between celiac disease and anorexia nervosa
The eating disorders study Dr. Kemper discussed examined possible associations between celiac disease and anorexia nervosa (Pediatrics. 2017. doi: 10.1542/peds.2016-4367). Researchers compared 17,959 Swedish females diagnosed with celiac disease between 1969 and 2008, at a median 28 years old, to 89,379 controls matched by sex and age.
Anorexia occurred more often among those with celiac disease than those without: a rate of 27 girls per 100,000 with celiac disease developed anorexia per year, compared with 18 of 100,000 without celiac disease, for a hazard ratio for an anorexia nervosa diagnosis of 1.46 (95% confidence interval, 1.08-1.98). In addition, girls whose celiac disease had not yet been identified had more than double the odds of developing anorexia before diagnosis than did those without celiac disease (odds ratio, 2.13).
Females with celiac disease therefore were more likely to have anorexia both before and after their celiac diagnosis, although the authors noted that surveillance bias may have made it more likely for either of the patients’ conditions to be identified after the first was. Another possible explanation is shared genetic risk factors, the authors wrote.
Dr. Kemper also offered possible reasons, including one related to the child behavior study.
“It could be that girls with celiac disease might develop anorexia because of the need to focus on their diet,” he said in an interview. “Celiac disease has been associated with psychological problems, and so that could contribute.”
Until further research can shed light on the reasons for the associations, physicians simply should be aware of the study’s clinical implications.
“Pediatricians should be aware of the bidirectional association between celiac disease and anorexia nervosa in teens and young adult women, and be prepared to evaluate for celiac disease or treat anorexia,” Dr. Kemper said.
He noted the need for more research to learn “what pediatricians can do to help to either prevent these problems from developing in the first place, or identify and treat celiac disease or anorexia nervosa early to prevent long-term complications.”
Dr. Kemper reported having no relevant financial disclosures and no external funding. Ketil Stordal, MD, PhD, of the anorexia study received funding from the OAK foundation in Switzerland, and Cynthia M. Bulik, PhD, from the same study received funding from the Swedish Research Council, and has consulted for and received a grant from Shire. The remaining authors of the anorexia study had no relevant financial disclosures. The behavioral study was funded by the National Institutes of Health, the Juvenile Diabetes Research Foundation and the Centers for Disease Control and Prevention. The authors from the behavioral study had no relevant financial disclosures.
FDA: No more codeine or hydrocodone cold medicines for children
New safety labeling changes for prescription cough and cold medicines containing codeine or hydrocodone limit their use to adults 18 years or older.
The Food and Drug Administration took this action after “conducting an extensive review and convening a panel of outside experts,” which determined that the risks of these medicines outweigh their benefits in children younger than 18 years. The agency also is requiring companies to add a boxed warning to drug labels for prescription cough and cold medicines containing codeine or hydrocodone about the “risks of misuse, abuse, addiction, overdose, death, and slowed or difficult breathing,” according to an FDA safety announcement.
Common side effects of opioids include drowsiness, dizziness, nausea, vomiting, constipation, shortness of breath, and headache, according to the press release.
Reassure parents that cough because of a cold or upper respiratory infection is self-limited and generally does not need to be treated, the FDA advised. If children do need cough treatment, there are over-the-counter products such as dextromethorphan, as well as prescription benzonatate products, the FDA said. Encourage parents to check labels of nonprescription cough and cold products.
In a few states, some codeine cough medicines are available OTC. The FDA is considering regulatory action for these products, according to the safety announcement.
New safety labeling changes for prescription cough and cold medicines containing codeine or hydrocodone limit their use to adults 18 years or older.
The Food and Drug Administration took this action after “conducting an extensive review and convening a panel of outside experts,” which determined that the risks of these medicines outweigh their benefits in children younger than 18 years. The agency also is requiring companies to add a boxed warning to drug labels for prescription cough and cold medicines containing codeine or hydrocodone about the “risks of misuse, abuse, addiction, overdose, death, and slowed or difficult breathing,” according to an FDA safety announcement.
Common side effects of opioids include drowsiness, dizziness, nausea, vomiting, constipation, shortness of breath, and headache, according to the press release.
Reassure parents that cough because of a cold or upper respiratory infection is self-limited and generally does not need to be treated, the FDA advised. If children do need cough treatment, there are over-the-counter products such as dextromethorphan, as well as prescription benzonatate products, the FDA said. Encourage parents to check labels of nonprescription cough and cold products.
In a few states, some codeine cough medicines are available OTC. The FDA is considering regulatory action for these products, according to the safety announcement.
New safety labeling changes for prescription cough and cold medicines containing codeine or hydrocodone limit their use to adults 18 years or older.
The Food and Drug Administration took this action after “conducting an extensive review and convening a panel of outside experts,” which determined that the risks of these medicines outweigh their benefits in children younger than 18 years. The agency also is requiring companies to add a boxed warning to drug labels for prescription cough and cold medicines containing codeine or hydrocodone about the “risks of misuse, abuse, addiction, overdose, death, and slowed or difficult breathing,” according to an FDA safety announcement.
Common side effects of opioids include drowsiness, dizziness, nausea, vomiting, constipation, shortness of breath, and headache, according to the press release.
Reassure parents that cough because of a cold or upper respiratory infection is self-limited and generally does not need to be treated, the FDA advised. If children do need cough treatment, there are over-the-counter products such as dextromethorphan, as well as prescription benzonatate products, the FDA said. Encourage parents to check labels of nonprescription cough and cold products.
In a few states, some codeine cough medicines are available OTC. The FDA is considering regulatory action for these products, according to the safety announcement.
DNA methylation may predict outcomes in JMML
New research suggests DNA methylation may be used to predict how children with juvenile myelomonocytic leukemia (JMML) will respond to treatment.
Researchers found they could divide patients into risk groups according to their methylation levels.
Patients with the highest methylation levels had the worst event-free survival, while patients who recovered spontaneously had methylation levels similar to those of healthy control subjects.
“This data provides important information that will help clinicians decide how intensively and swiftly to treat their patients,” said Mignon Loh, MD, of Benioff Children’s Hospital, University of California, San Francisco.
She and her colleagues described this research in Nature Communications.
The team studied genome-wide DNA methylation levels in an initial group of 39 patients with JMML and then validated the results in a group of 40 JMML patients.
Statistical analysis revealed that patients fell into 3 clusters with high, intermediate, or low levels of DNA methylation. And patients’ methylation levels were associated with 4-year event-free survival.
In the initial cohort, 6% (1/15) of patients in the lowest methylation group had an event at 4 years, as did 45% (5/11) of patients with intermediate levels of methylation and 61% (8/13) of patients with the highest levels of methylation.
In the validation cohort, 8% (1/12) of patients in the lowest methylation group had an event at 4 years, as did 36% (4/11) of patients with intermediate levels of methylation and 76% (13/17) of patients with the highest levels of methylation.
“For us, this was surprising,” said study author Elliot Stieglitz, MD, also of Benioff Children’s Hospital.
“We are not yet able to say why DNA methylation is different amongst these patients, but for it to be so predictive of outcomes, even more than genetic mutations, was a big surprise.”
The researchers also found that methylation levels might predict spontaneous remission as well.
Thirteen of the 14 patients who had spontaneous remission clustered together. And their DNA methylation levels were closer to those of healthy control subjects than those of other JMML cases.
“Because we have never been able to tell which patients might spontaneously recover, and because the disease can be so aggressive, the standard of care has been to recommend transplants for everybody,” Dr Stieglitz said.
“There are many health risks associated with bone marrow transplants, ranging from infections to long-term short stature and even death in some cases. To be able to avoid this intensive intervention for some patients based on a methylation assay would really be cutting-edge clinical science.” 
New research suggests DNA methylation may be used to predict how children with juvenile myelomonocytic leukemia (JMML) will respond to treatment.
Researchers found they could divide patients into risk groups according to their methylation levels.
Patients with the highest methylation levels had the worst event-free survival, while patients who recovered spontaneously had methylation levels similar to those of healthy control subjects.
“This data provides important information that will help clinicians decide how intensively and swiftly to treat their patients,” said Mignon Loh, MD, of Benioff Children’s Hospital, University of California, San Francisco.
She and her colleagues described this research in Nature Communications.
The team studied genome-wide DNA methylation levels in an initial group of 39 patients with JMML and then validated the results in a group of 40 JMML patients.
Statistical analysis revealed that patients fell into 3 clusters with high, intermediate, or low levels of DNA methylation. And patients’ methylation levels were associated with 4-year event-free survival.
In the initial cohort, 6% (1/15) of patients in the lowest methylation group had an event at 4 years, as did 45% (5/11) of patients with intermediate levels of methylation and 61% (8/13) of patients with the highest levels of methylation.
In the validation cohort, 8% (1/12) of patients in the lowest methylation group had an event at 4 years, as did 36% (4/11) of patients with intermediate levels of methylation and 76% (13/17) of patients with the highest levels of methylation.
“For us, this was surprising,” said study author Elliot Stieglitz, MD, also of Benioff Children’s Hospital.
“We are not yet able to say why DNA methylation is different amongst these patients, but for it to be so predictive of outcomes, even more than genetic mutations, was a big surprise.”
The researchers also found that methylation levels might predict spontaneous remission as well.
Thirteen of the 14 patients who had spontaneous remission clustered together. And their DNA methylation levels were closer to those of healthy control subjects than those of other JMML cases.
“Because we have never been able to tell which patients might spontaneously recover, and because the disease can be so aggressive, the standard of care has been to recommend transplants for everybody,” Dr Stieglitz said.
“There are many health risks associated with bone marrow transplants, ranging from infections to long-term short stature and even death in some cases. To be able to avoid this intensive intervention for some patients based on a methylation assay would really be cutting-edge clinical science.”
New research suggests DNA methylation may be used to predict how children with juvenile myelomonocytic leukemia (JMML) will respond to treatment.
Researchers found they could divide patients into risk groups according to their methylation levels.
Patients with the highest methylation levels had the worst event-free survival, while patients who recovered spontaneously had methylation levels similar to those of healthy control subjects.
“This data provides important information that will help clinicians decide how intensively and swiftly to treat their patients,” said Mignon Loh, MD, of Benioff Children’s Hospital, University of California, San Francisco.
She and her colleagues described this research in Nature Communications.
The team studied genome-wide DNA methylation levels in an initial group of 39 patients with JMML and then validated the results in a group of 40 JMML patients.
Statistical analysis revealed that patients fell into 3 clusters with high, intermediate, or low levels of DNA methylation. And patients’ methylation levels were associated with 4-year event-free survival.
In the initial cohort, 6% (1/15) of patients in the lowest methylation group had an event at 4 years, as did 45% (5/11) of patients with intermediate levels of methylation and 61% (8/13) of patients with the highest levels of methylation.
In the validation cohort, 8% (1/12) of patients in the lowest methylation group had an event at 4 years, as did 36% (4/11) of patients with intermediate levels of methylation and 76% (13/17) of patients with the highest levels of methylation.
“For us, this was surprising,” said study author Elliot Stieglitz, MD, also of Benioff Children’s Hospital.
“We are not yet able to say why DNA methylation is different amongst these patients, but for it to be so predictive of outcomes, even more than genetic mutations, was a big surprise.”
The researchers also found that methylation levels might predict spontaneous remission as well.
Thirteen of the 14 patients who had spontaneous remission clustered together. And their DNA methylation levels were closer to those of healthy control subjects than those of other JMML cases.
“Because we have never been able to tell which patients might spontaneously recover, and because the disease can be so aggressive, the standard of care has been to recommend transplants for everybody,” Dr Stieglitz said.
“There are many health risks associated with bone marrow transplants, ranging from infections to long-term short stature and even death in some cases. To be able to avoid this intensive intervention for some patients based on a methylation assay would really be cutting-edge clinical science.”