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Q.N.S.
In the early 1970’s, the three letters that a pediatric house officer hated to see on a slip returning from the lab were Q.N.S. Quality Not Sufficient meant that the minutes, which seemed like hours, you had invested torturing some poor sick child to obtain just a few cc’s of blood had been wasted. It also meant returning to the patient’s crib or bedside to explain to the child and her parents that the torture you had promised was over for the day was in fact not over.
Tourniquets were fished out of lapel buttonholes, and the search for a decent vein had to begin all over again. If the child was chubby or bloated with retained fluid, those veins were invisible. If the child had been ill for weeks – particularly if the patient had been on chemotherapy – all of the good veins had been blown or had clotted days ago.
Many of the patients were saintly and eerily cooperative despite your fumbling attempts at venipuncture, but most were not. Some parents were so supportive of your efforts that you wanted to hug them when the ordeal was over (and you did). A few parents amped up the tension at the bedside so much that you wanted to ask them to leave (but you didn’t). If a parent was understandably incapable of effectively restraining the child, you needed to find an experienced nurse to help. A few of the best nurses were so good that the house officer merely needed to hold the needle still, and the child was repositioned in just the right orientation so that the puncture occurred miraculously.
There were some last ditch efforts at phlebotomy that were so ghastly that you had to ask the parents to leave. I don’t know if the infamous internal jugular stick is still used, but it wasn’t pretty. And it was almost as frightening for the physician holding the needle as it was for the patient. Even in the big teaching hospitals, dedicated phlebotomists hadn’t been invented yet. A few nurses had earned reputations as good vein finders, but for the most part it was on-the-job training for the house officers.
It was not until 1973 that Dr. John Broviac’s central line catheters became available in some hospitals and 1979 until Dr. Robert Hickman’s version appeared. It took a few more years before techniques were perfected for safely drawing specimens from these lines that had been originally intended for infusion. But for me and my cohort of house officers and our unfortunate patients, it was years too late. I am sure that caring for hospitalized pediatric cancer patients today continues to be dominated by challenges. But for those of us tasked with drawing blood from patients without the benefit of central line catheters, it was gut wrenching.
Those battles for a few cc’s of blood left their scars. I have seldom ordered any blood test without asking myself whether there wasn’t a bloodless way of assessing the patient’s condition. Or couldn’t we just do the test on a drop or two of blood? Of course, as I as finishing my training, more tests were downsized so that they could be done “micro.” But as you know, getting enough blood from a heel stick or finger prick isn’t always as easy as it sounds. If the child is shocky or cold, a good blood flow is hard to obtain. Warming helps but squeezing doesn’t because tissue juices can dilute the sample, and the trauma of squeezing can contaminate the sample.
A study published in the American Journal of Clinical Pathology raises the question of how accurately even a single drop of blood reflects what is going on in the patient’s total blood pool (“Drop by drop variation in the cellular components of fingerprick blood: Implications for point-of-care diagnostic development” [Am J Clin Pathol. 2015 Dec;144(6):885-94]). Two bioengineers from Rice University discovered that six successive drops of blood from a single finger prick varied by a significant amount when analyzed for a variety of cellular components. For example, the drop-to-drop variability for hemoglobin was five times that of a sample collected by venipuncture.
You and I may dream of the day when just a drop will do it and we can put our needles away for good. Unfortunately, for now, the answer is that a single drop of blood is a Q.N.S.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”
In the early 1970’s, the three letters that a pediatric house officer hated to see on a slip returning from the lab were Q.N.S. Quality Not Sufficient meant that the minutes, which seemed like hours, you had invested torturing some poor sick child to obtain just a few cc’s of blood had been wasted. It also meant returning to the patient’s crib or bedside to explain to the child and her parents that the torture you had promised was over for the day was in fact not over.
Tourniquets were fished out of lapel buttonholes, and the search for a decent vein had to begin all over again. If the child was chubby or bloated with retained fluid, those veins were invisible. If the child had been ill for weeks – particularly if the patient had been on chemotherapy – all of the good veins had been blown or had clotted days ago.
Many of the patients were saintly and eerily cooperative despite your fumbling attempts at venipuncture, but most were not. Some parents were so supportive of your efforts that you wanted to hug them when the ordeal was over (and you did). A few parents amped up the tension at the bedside so much that you wanted to ask them to leave (but you didn’t). If a parent was understandably incapable of effectively restraining the child, you needed to find an experienced nurse to help. A few of the best nurses were so good that the house officer merely needed to hold the needle still, and the child was repositioned in just the right orientation so that the puncture occurred miraculously.
There were some last ditch efforts at phlebotomy that were so ghastly that you had to ask the parents to leave. I don’t know if the infamous internal jugular stick is still used, but it wasn’t pretty. And it was almost as frightening for the physician holding the needle as it was for the patient. Even in the big teaching hospitals, dedicated phlebotomists hadn’t been invented yet. A few nurses had earned reputations as good vein finders, but for the most part it was on-the-job training for the house officers.
It was not until 1973 that Dr. John Broviac’s central line catheters became available in some hospitals and 1979 until Dr. Robert Hickman’s version appeared. It took a few more years before techniques were perfected for safely drawing specimens from these lines that had been originally intended for infusion. But for me and my cohort of house officers and our unfortunate patients, it was years too late. I am sure that caring for hospitalized pediatric cancer patients today continues to be dominated by challenges. But for those of us tasked with drawing blood from patients without the benefit of central line catheters, it was gut wrenching.
Those battles for a few cc’s of blood left their scars. I have seldom ordered any blood test without asking myself whether there wasn’t a bloodless way of assessing the patient’s condition. Or couldn’t we just do the test on a drop or two of blood? Of course, as I as finishing my training, more tests were downsized so that they could be done “micro.” But as you know, getting enough blood from a heel stick or finger prick isn’t always as easy as it sounds. If the child is shocky or cold, a good blood flow is hard to obtain. Warming helps but squeezing doesn’t because tissue juices can dilute the sample, and the trauma of squeezing can contaminate the sample.
A study published in the American Journal of Clinical Pathology raises the question of how accurately even a single drop of blood reflects what is going on in the patient’s total blood pool (“Drop by drop variation in the cellular components of fingerprick blood: Implications for point-of-care diagnostic development” [Am J Clin Pathol. 2015 Dec;144(6):885-94]). Two bioengineers from Rice University discovered that six successive drops of blood from a single finger prick varied by a significant amount when analyzed for a variety of cellular components. For example, the drop-to-drop variability for hemoglobin was five times that of a sample collected by venipuncture.
You and I may dream of the day when just a drop will do it and we can put our needles away for good. Unfortunately, for now, the answer is that a single drop of blood is a Q.N.S.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”
In the early 1970’s, the three letters that a pediatric house officer hated to see on a slip returning from the lab were Q.N.S. Quality Not Sufficient meant that the minutes, which seemed like hours, you had invested torturing some poor sick child to obtain just a few cc’s of blood had been wasted. It also meant returning to the patient’s crib or bedside to explain to the child and her parents that the torture you had promised was over for the day was in fact not over.
Tourniquets were fished out of lapel buttonholes, and the search for a decent vein had to begin all over again. If the child was chubby or bloated with retained fluid, those veins were invisible. If the child had been ill for weeks – particularly if the patient had been on chemotherapy – all of the good veins had been blown or had clotted days ago.
Many of the patients were saintly and eerily cooperative despite your fumbling attempts at venipuncture, but most were not. Some parents were so supportive of your efforts that you wanted to hug them when the ordeal was over (and you did). A few parents amped up the tension at the bedside so much that you wanted to ask them to leave (but you didn’t). If a parent was understandably incapable of effectively restraining the child, you needed to find an experienced nurse to help. A few of the best nurses were so good that the house officer merely needed to hold the needle still, and the child was repositioned in just the right orientation so that the puncture occurred miraculously.
There were some last ditch efforts at phlebotomy that were so ghastly that you had to ask the parents to leave. I don’t know if the infamous internal jugular stick is still used, but it wasn’t pretty. And it was almost as frightening for the physician holding the needle as it was for the patient. Even in the big teaching hospitals, dedicated phlebotomists hadn’t been invented yet. A few nurses had earned reputations as good vein finders, but for the most part it was on-the-job training for the house officers.
It was not until 1973 that Dr. John Broviac’s central line catheters became available in some hospitals and 1979 until Dr. Robert Hickman’s version appeared. It took a few more years before techniques were perfected for safely drawing specimens from these lines that had been originally intended for infusion. But for me and my cohort of house officers and our unfortunate patients, it was years too late. I am sure that caring for hospitalized pediatric cancer patients today continues to be dominated by challenges. But for those of us tasked with drawing blood from patients without the benefit of central line catheters, it was gut wrenching.
Those battles for a few cc’s of blood left their scars. I have seldom ordered any blood test without asking myself whether there wasn’t a bloodless way of assessing the patient’s condition. Or couldn’t we just do the test on a drop or two of blood? Of course, as I as finishing my training, more tests were downsized so that they could be done “micro.” But as you know, getting enough blood from a heel stick or finger prick isn’t always as easy as it sounds. If the child is shocky or cold, a good blood flow is hard to obtain. Warming helps but squeezing doesn’t because tissue juices can dilute the sample, and the trauma of squeezing can contaminate the sample.
A study published in the American Journal of Clinical Pathology raises the question of how accurately even a single drop of blood reflects what is going on in the patient’s total blood pool (“Drop by drop variation in the cellular components of fingerprick blood: Implications for point-of-care diagnostic development” [Am J Clin Pathol. 2015 Dec;144(6):885-94]). Two bioengineers from Rice University discovered that six successive drops of blood from a single finger prick varied by a significant amount when analyzed for a variety of cellular components. For example, the drop-to-drop variability for hemoglobin was five times that of a sample collected by venipuncture.
You and I may dream of the day when just a drop will do it and we can put our needles away for good. Unfortunately, for now, the answer is that a single drop of blood is a Q.N.S.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”
Study: 2.6% of patients discharged from U.S. hospital used probiotics
Probiotics were used by 2.6% of patients who had been discharged from 145 U.S. hospitals in 2012, according to an analysis of data by Sarah H. Yi of the Centers for Disease Control and Prevention and her colleagues.
“Whether probiotics are effective in preserving or restoring a healthy microbiome remains unknown, but the high prevalence of probiotic use among hospitalized patients may indicate a growing belief among clinicians that these agents may be an effective strategy for doing so,” Ms. Yi and her colleagues wrote.
The researchers used information contained in the Truven Health MarketScan Hospital Drug Database to estimate probiotic use in the inpatient setting.
Among 1,976,167 pediatric and adult patients discharged from 145 hospitals in 2012, 51,723 (2.6%) of the patients used probiotics. The individuals who used probiotics had been patients at 139 of the 145 hospitals. Compared with patients who had not used probiotics, the patients who had used probiotics were 21 times more likely to have a discharge diagnosis of Clostridium difficile infection (P less than .0001), almost 9 times more likely to have used antimicrobials (P less than .0001), more likely to have been admitted from another inpatient health care facility (P less than .0001), and more likely to have been transferred to another health care facility at discharge (P less than .001). Each of the probiotic formulations used contained between one and four organisms identified at the species level. Saccharomyces boulardii, Lactobacillus acidophilus, L. bulgaricus, and L. rhamnosus were the most commonly used probiotic formulations.
The top five diagnoses for the patients who received probiotics were septicemia (except in labor); pneumonia (except that caused by tuberculosis or sexually transmitted disease); intestinal infection; skin and subcutaneous tissue infections; and urinary tract infections. For those patients not taking probiotics, live-born infants, osteoarthritis, septicemia (except during labor), pneumonia (except that caused by tuberculosis or sexually transmitted disease), and heart failure (nonhypertensive) were the most commonly received diagnoses.
The researchers also analyzed a study of the use of probiotics at 60 hospitals during 2006-2012, which showed annual increases of probiotic use among discharged patients and an overall 2.9-fold increase in probiotic use during those years. Specifically, 10,722 discharged patients used probiotics in 2006, compared with 28,871 patients in 2012.
“Because the patients most likely to benefit [from probiotic use] are also most at risk for an adverse event, preclinical research focused on the selection of likely probiotics and carefully designed clinical trials with systematic assessment of safety is particularly important,” the researchers said.
Among the questions needed to addressed in future research on probiotic use is “which strain-specific organisms, which patient populations, at what doses, and in what time frames (related to antibiotic use in particular) are both safe and effective in the prevention or treatment of which diseases?” according to the researchers.
Read the study in American Journal of Infection Control (doi: 10.1016/j.ajic.2015.12.001).
Probiotics were used by 2.6% of patients who had been discharged from 145 U.S. hospitals in 2012, according to an analysis of data by Sarah H. Yi of the Centers for Disease Control and Prevention and her colleagues.
“Whether probiotics are effective in preserving or restoring a healthy microbiome remains unknown, but the high prevalence of probiotic use among hospitalized patients may indicate a growing belief among clinicians that these agents may be an effective strategy for doing so,” Ms. Yi and her colleagues wrote.
The researchers used information contained in the Truven Health MarketScan Hospital Drug Database to estimate probiotic use in the inpatient setting.
Among 1,976,167 pediatric and adult patients discharged from 145 hospitals in 2012, 51,723 (2.6%) of the patients used probiotics. The individuals who used probiotics had been patients at 139 of the 145 hospitals. Compared with patients who had not used probiotics, the patients who had used probiotics were 21 times more likely to have a discharge diagnosis of Clostridium difficile infection (P less than .0001), almost 9 times more likely to have used antimicrobials (P less than .0001), more likely to have been admitted from another inpatient health care facility (P less than .0001), and more likely to have been transferred to another health care facility at discharge (P less than .001). Each of the probiotic formulations used contained between one and four organisms identified at the species level. Saccharomyces boulardii, Lactobacillus acidophilus, L. bulgaricus, and L. rhamnosus were the most commonly used probiotic formulations.
The top five diagnoses for the patients who received probiotics were septicemia (except in labor); pneumonia (except that caused by tuberculosis or sexually transmitted disease); intestinal infection; skin and subcutaneous tissue infections; and urinary tract infections. For those patients not taking probiotics, live-born infants, osteoarthritis, septicemia (except during labor), pneumonia (except that caused by tuberculosis or sexually transmitted disease), and heart failure (nonhypertensive) were the most commonly received diagnoses.
The researchers also analyzed a study of the use of probiotics at 60 hospitals during 2006-2012, which showed annual increases of probiotic use among discharged patients and an overall 2.9-fold increase in probiotic use during those years. Specifically, 10,722 discharged patients used probiotics in 2006, compared with 28,871 patients in 2012.
“Because the patients most likely to benefit [from probiotic use] are also most at risk for an adverse event, preclinical research focused on the selection of likely probiotics and carefully designed clinical trials with systematic assessment of safety is particularly important,” the researchers said.
Among the questions needed to addressed in future research on probiotic use is “which strain-specific organisms, which patient populations, at what doses, and in what time frames (related to antibiotic use in particular) are both safe and effective in the prevention or treatment of which diseases?” according to the researchers.
Read the study in American Journal of Infection Control (doi: 10.1016/j.ajic.2015.12.001).
Probiotics were used by 2.6% of patients who had been discharged from 145 U.S. hospitals in 2012, according to an analysis of data by Sarah H. Yi of the Centers for Disease Control and Prevention and her colleagues.
“Whether probiotics are effective in preserving or restoring a healthy microbiome remains unknown, but the high prevalence of probiotic use among hospitalized patients may indicate a growing belief among clinicians that these agents may be an effective strategy for doing so,” Ms. Yi and her colleagues wrote.
The researchers used information contained in the Truven Health MarketScan Hospital Drug Database to estimate probiotic use in the inpatient setting.
Among 1,976,167 pediatric and adult patients discharged from 145 hospitals in 2012, 51,723 (2.6%) of the patients used probiotics. The individuals who used probiotics had been patients at 139 of the 145 hospitals. Compared with patients who had not used probiotics, the patients who had used probiotics were 21 times more likely to have a discharge diagnosis of Clostridium difficile infection (P less than .0001), almost 9 times more likely to have used antimicrobials (P less than .0001), more likely to have been admitted from another inpatient health care facility (P less than .0001), and more likely to have been transferred to another health care facility at discharge (P less than .001). Each of the probiotic formulations used contained between one and four organisms identified at the species level. Saccharomyces boulardii, Lactobacillus acidophilus, L. bulgaricus, and L. rhamnosus were the most commonly used probiotic formulations.
The top five diagnoses for the patients who received probiotics were septicemia (except in labor); pneumonia (except that caused by tuberculosis or sexually transmitted disease); intestinal infection; skin and subcutaneous tissue infections; and urinary tract infections. For those patients not taking probiotics, live-born infants, osteoarthritis, septicemia (except during labor), pneumonia (except that caused by tuberculosis or sexually transmitted disease), and heart failure (nonhypertensive) were the most commonly received diagnoses.
The researchers also analyzed a study of the use of probiotics at 60 hospitals during 2006-2012, which showed annual increases of probiotic use among discharged patients and an overall 2.9-fold increase in probiotic use during those years. Specifically, 10,722 discharged patients used probiotics in 2006, compared with 28,871 patients in 2012.
“Because the patients most likely to benefit [from probiotic use] are also most at risk for an adverse event, preclinical research focused on the selection of likely probiotics and carefully designed clinical trials with systematic assessment of safety is particularly important,” the researchers said.
Among the questions needed to addressed in future research on probiotic use is “which strain-specific organisms, which patient populations, at what doses, and in what time frames (related to antibiotic use in particular) are both safe and effective in the prevention or treatment of which diseases?” according to the researchers.
Read the study in American Journal of Infection Control (doi: 10.1016/j.ajic.2015.12.001).
FROM AMERICAN JOURNAL OF INFECTION CONTROL
Socially supported transgender children exhibit positive mental health
Transgender children who receive support for their gender identity are no more likely to be depressed than are other children and had only slightly higher anxiety symptoms, a recent study found.
“Critically, transgender children supported in their identities had internalizing symptoms that were well below even the preclinical range,” reported Kristina R. Olson, Ph.D., and her associates in the department of psychology at the University of (Seattle) Washington (Pediatrics 2016 Feb 19. doi: 10.1542/peds.2015-3223). “These findings suggest that familial support in general, or specifically via the decision to allow their children to socially transition, may be associated with better mental health outcomes among transgender children.”
The authors recruited 73 transgender children between the ages of 3 and 12 years. All the children identified as a gender different from the sex they were assigned at birth, used the pronouns associated with that gender, and presented in that gender in all social situations, including during everyday life, at school, and at home. Among the 22 born-females and 51 born-males, the average age of the children was 8 years.
The researchers compared these children’s mental health to that of 49 of their siblings and 73 age-matched control children with no history of cross-gender behavior. Approximately three quarters of the children across all three groups were white, and smaller numbers of children were Hispanic, Asian, or multiracial. Nearly all the children lived in homes with an annual family income above $75,000, and about half lived in homes with an annual income over $125,000.
Parents filled out assessments of their children’s symptoms of depression and anxiety. Scores for transgender children were similar to those of the general population in terms of depression and only slightly elevated for anxiety, although still below even the subclinical range. No statistical differences in depression symptoms existed between the transgender children and either their siblings or the control children, and again, anxiety levels were only slightly increased.
The authors point out that most previous studies of mental health among transgender people have focused on teens and adults and have consistently found “dramatically elevated rates of anxiety, depression and suicidality among transgender people.” These findings likely reflect “years of prejudice, discrimination, and stigma; conflict between one’s appearance and stated identity; and general rejection by people in their social environments, including their families,” Dr. Olson and her associates wrote. “There is now growing evidence that social support is linked to better mental health outcomes among transgender adolescents and adults.”
The findings of this study reveal that “socially transitioned transgender children showed substantially lower rates of internalizing symptoms than children with gender identity disorder reported in previous studies,” they said. “Allowing children to present in everyday life as their gender identity rather than their natal sex is associated with developmentally normative levels of depression and anxiety.”
A significant potential limitation of this study, however, is that the children transitioned at a young age when such transitions tend to be controversial and “yet did so anyway,” Dr. Olson and her associates pointed out. “Surely not all families with transgender children make this decision, meaning there are likely characteristics that are unique to these families,” they wrote. “In addition, the transgender children in this study all socially transitioned much earlier than nearly all transgender adults alive today in the United States and Canada.” The reasons for this also may play a role in the findings.
The Royalty Research Fund at the University of Washington, the National Institute of Mental Health, and the National Institutes of Health funded the research. The authors reported no relevant financial disclosures.
In this issue of Pediatrics, Olson and colleagues provide evidence in support of social transition, a completely reversible intervention associated with lower rates of depression and anxiety in transgender prepubescent children. Socially transitioned children, or those who have adopted the name, hairstyle, clothing, and pronoun associated with their affirmed, rather than birth gender, have become more visible in the media over the last several years. Although to date there has been no published evidence to support providers in suggesting social transition as a beneficial intervention, many families, often guided by mental health professionals, make that decision based on observational evidence in response to seeing how suffering can be alleviated by allowing the children to express their own sense of gender.
The rationale cited by those who oppose social transition are that children cannot possibly know their gender at such an early age and that social transition could encourage children to later seek out treatment of medical transition. Proponents have argued that social transition is useful both in improving function in those children who are intensely gender dysphoric and in helping to test the waters so to speak; that is, giving the child a completely reversible way to explore life in the other gender before committing to any medical interventions.
Olson and colleagues give supporters of social transition evidence that shows what we have suspected all along: that socially transitioned children are doing fine, or at least as well as their age-matched peers and siblings. This finding is truly stunning in light of the numerous studies that show depression and anxiety internalizing psychopathology scores up to three times higher for non–socially transitioned children. Although it does not establish a causal relationship, this finding is crucially important to professionals who work with these children, as well as their families, in showing us that they are not likely to suffer any additional harm and may benefit from early social transition.
These comments were excerpted from a commentary by Dr. Ilana Sherer of the Palo Alto Medical Foundation in Dublin, Calif., and the Child and Adolescent Gender Center at Benioff Children’s Hospital at the University of California, San Fransisco (Pediatrics 2016 Feb 19. doi: 10.1542/peds.2015-4358). The author reported no external funding and no relevant financial disclosures.
In this issue of Pediatrics, Olson and colleagues provide evidence in support of social transition, a completely reversible intervention associated with lower rates of depression and anxiety in transgender prepubescent children. Socially transitioned children, or those who have adopted the name, hairstyle, clothing, and pronoun associated with their affirmed, rather than birth gender, have become more visible in the media over the last several years. Although to date there has been no published evidence to support providers in suggesting social transition as a beneficial intervention, many families, often guided by mental health professionals, make that decision based on observational evidence in response to seeing how suffering can be alleviated by allowing the children to express their own sense of gender.
The rationale cited by those who oppose social transition are that children cannot possibly know their gender at such an early age and that social transition could encourage children to later seek out treatment of medical transition. Proponents have argued that social transition is useful both in improving function in those children who are intensely gender dysphoric and in helping to test the waters so to speak; that is, giving the child a completely reversible way to explore life in the other gender before committing to any medical interventions.
Olson and colleagues give supporters of social transition evidence that shows what we have suspected all along: that socially transitioned children are doing fine, or at least as well as their age-matched peers and siblings. This finding is truly stunning in light of the numerous studies that show depression and anxiety internalizing psychopathology scores up to three times higher for non–socially transitioned children. Although it does not establish a causal relationship, this finding is crucially important to professionals who work with these children, as well as their families, in showing us that they are not likely to suffer any additional harm and may benefit from early social transition.
These comments were excerpted from a commentary by Dr. Ilana Sherer of the Palo Alto Medical Foundation in Dublin, Calif., and the Child and Adolescent Gender Center at Benioff Children’s Hospital at the University of California, San Fransisco (Pediatrics 2016 Feb 19. doi: 10.1542/peds.2015-4358). The author reported no external funding and no relevant financial disclosures.
In this issue of Pediatrics, Olson and colleagues provide evidence in support of social transition, a completely reversible intervention associated with lower rates of depression and anxiety in transgender prepubescent children. Socially transitioned children, or those who have adopted the name, hairstyle, clothing, and pronoun associated with their affirmed, rather than birth gender, have become more visible in the media over the last several years. Although to date there has been no published evidence to support providers in suggesting social transition as a beneficial intervention, many families, often guided by mental health professionals, make that decision based on observational evidence in response to seeing how suffering can be alleviated by allowing the children to express their own sense of gender.
The rationale cited by those who oppose social transition are that children cannot possibly know their gender at such an early age and that social transition could encourage children to later seek out treatment of medical transition. Proponents have argued that social transition is useful both in improving function in those children who are intensely gender dysphoric and in helping to test the waters so to speak; that is, giving the child a completely reversible way to explore life in the other gender before committing to any medical interventions.
Olson and colleagues give supporters of social transition evidence that shows what we have suspected all along: that socially transitioned children are doing fine, or at least as well as their age-matched peers and siblings. This finding is truly stunning in light of the numerous studies that show depression and anxiety internalizing psychopathology scores up to three times higher for non–socially transitioned children. Although it does not establish a causal relationship, this finding is crucially important to professionals who work with these children, as well as their families, in showing us that they are not likely to suffer any additional harm and may benefit from early social transition.
These comments were excerpted from a commentary by Dr. Ilana Sherer of the Palo Alto Medical Foundation in Dublin, Calif., and the Child and Adolescent Gender Center at Benioff Children’s Hospital at the University of California, San Fransisco (Pediatrics 2016 Feb 19. doi: 10.1542/peds.2015-4358). The author reported no external funding and no relevant financial disclosures.
Transgender children who receive support for their gender identity are no more likely to be depressed than are other children and had only slightly higher anxiety symptoms, a recent study found.
“Critically, transgender children supported in their identities had internalizing symptoms that were well below even the preclinical range,” reported Kristina R. Olson, Ph.D., and her associates in the department of psychology at the University of (Seattle) Washington (Pediatrics 2016 Feb 19. doi: 10.1542/peds.2015-3223). “These findings suggest that familial support in general, or specifically via the decision to allow their children to socially transition, may be associated with better mental health outcomes among transgender children.”
The authors recruited 73 transgender children between the ages of 3 and 12 years. All the children identified as a gender different from the sex they were assigned at birth, used the pronouns associated with that gender, and presented in that gender in all social situations, including during everyday life, at school, and at home. Among the 22 born-females and 51 born-males, the average age of the children was 8 years.
The researchers compared these children’s mental health to that of 49 of their siblings and 73 age-matched control children with no history of cross-gender behavior. Approximately three quarters of the children across all three groups were white, and smaller numbers of children were Hispanic, Asian, or multiracial. Nearly all the children lived in homes with an annual family income above $75,000, and about half lived in homes with an annual income over $125,000.
Parents filled out assessments of their children’s symptoms of depression and anxiety. Scores for transgender children were similar to those of the general population in terms of depression and only slightly elevated for anxiety, although still below even the subclinical range. No statistical differences in depression symptoms existed between the transgender children and either their siblings or the control children, and again, anxiety levels were only slightly increased.
The authors point out that most previous studies of mental health among transgender people have focused on teens and adults and have consistently found “dramatically elevated rates of anxiety, depression and suicidality among transgender people.” These findings likely reflect “years of prejudice, discrimination, and stigma; conflict between one’s appearance and stated identity; and general rejection by people in their social environments, including their families,” Dr. Olson and her associates wrote. “There is now growing evidence that social support is linked to better mental health outcomes among transgender adolescents and adults.”
The findings of this study reveal that “socially transitioned transgender children showed substantially lower rates of internalizing symptoms than children with gender identity disorder reported in previous studies,” they said. “Allowing children to present in everyday life as their gender identity rather than their natal sex is associated with developmentally normative levels of depression and anxiety.”
A significant potential limitation of this study, however, is that the children transitioned at a young age when such transitions tend to be controversial and “yet did so anyway,” Dr. Olson and her associates pointed out. “Surely not all families with transgender children make this decision, meaning there are likely characteristics that are unique to these families,” they wrote. “In addition, the transgender children in this study all socially transitioned much earlier than nearly all transgender adults alive today in the United States and Canada.” The reasons for this also may play a role in the findings.
The Royalty Research Fund at the University of Washington, the National Institute of Mental Health, and the National Institutes of Health funded the research. The authors reported no relevant financial disclosures.
Transgender children who receive support for their gender identity are no more likely to be depressed than are other children and had only slightly higher anxiety symptoms, a recent study found.
“Critically, transgender children supported in their identities had internalizing symptoms that were well below even the preclinical range,” reported Kristina R. Olson, Ph.D., and her associates in the department of psychology at the University of (Seattle) Washington (Pediatrics 2016 Feb 19. doi: 10.1542/peds.2015-3223). “These findings suggest that familial support in general, or specifically via the decision to allow their children to socially transition, may be associated with better mental health outcomes among transgender children.”
The authors recruited 73 transgender children between the ages of 3 and 12 years. All the children identified as a gender different from the sex they were assigned at birth, used the pronouns associated with that gender, and presented in that gender in all social situations, including during everyday life, at school, and at home. Among the 22 born-females and 51 born-males, the average age of the children was 8 years.
The researchers compared these children’s mental health to that of 49 of their siblings and 73 age-matched control children with no history of cross-gender behavior. Approximately three quarters of the children across all three groups were white, and smaller numbers of children were Hispanic, Asian, or multiracial. Nearly all the children lived in homes with an annual family income above $75,000, and about half lived in homes with an annual income over $125,000.
Parents filled out assessments of their children’s symptoms of depression and anxiety. Scores for transgender children were similar to those of the general population in terms of depression and only slightly elevated for anxiety, although still below even the subclinical range. No statistical differences in depression symptoms existed between the transgender children and either their siblings or the control children, and again, anxiety levels were only slightly increased.
The authors point out that most previous studies of mental health among transgender people have focused on teens and adults and have consistently found “dramatically elevated rates of anxiety, depression and suicidality among transgender people.” These findings likely reflect “years of prejudice, discrimination, and stigma; conflict between one’s appearance and stated identity; and general rejection by people in their social environments, including their families,” Dr. Olson and her associates wrote. “There is now growing evidence that social support is linked to better mental health outcomes among transgender adolescents and adults.”
The findings of this study reveal that “socially transitioned transgender children showed substantially lower rates of internalizing symptoms than children with gender identity disorder reported in previous studies,” they said. “Allowing children to present in everyday life as their gender identity rather than their natal sex is associated with developmentally normative levels of depression and anxiety.”
A significant potential limitation of this study, however, is that the children transitioned at a young age when such transitions tend to be controversial and “yet did so anyway,” Dr. Olson and her associates pointed out. “Surely not all families with transgender children make this decision, meaning there are likely characteristics that are unique to these families,” they wrote. “In addition, the transgender children in this study all socially transitioned much earlier than nearly all transgender adults alive today in the United States and Canada.” The reasons for this also may play a role in the findings.
The Royalty Research Fund at the University of Washington, the National Institute of Mental Health, and the National Institutes of Health funded the research. The authors reported no relevant financial disclosures.
FROM PEDIATRICS
Key clinical point: Transgender children can have positive mental health outcomes when supported in their gender.
Major finding: Depression symptoms were similar among transgender and nontransgender children, and anxiety symptoms were slightly higher but under preclinical ranges for transgender children.
Data source: A cross-sectional study of 73 transgender children aged 3-12 years from the Seattle area who consistently present in a gender opposite their natal sex in all social contexts, compared with 49 siblings and 73 control children.
Disclosures: The Royalty Research Fund at the University of Washington, the National Institute of Mental Health, and the National Institutes of Health funded the research. The authors reported no relevant financial disclosures.
Practice pathway addresses problem behaviors for children with ASD
A new practice pathway provides primary care providers with evidence-based steps in assessing and addressing irritability and problem behavior in patients at least 3 years old who have been diagnosed with an autism spectrum disorder (ASD).
“As the medical professionals whom children with ASD will probably encounter first and most frequently, pediatric primary care providers need a breadth of knowledge to enable them to identify contributing factors to irritability and problem behavior, decide when and how to initiate treatment, and judge when to refer to specialists,” reported Dr. Kelly McGuire of Columbia University Medical Center and New York State Psychiatric Institute, and her associates (Pediatrics. 2016 Feb;137 Suppl 2:S136-48). “Therefore, this practice pathway can be viewed more as a comprehensive rather than an exhaustive recommendation for [primary care physicians], who must weigh their expertise and resources when addressing the range of issues that a child with ASD and irritability and problem behavior may present.”
The Irritability Workgroup comprised eight child psychiatrists, a developmental pediatrician, and a behavioral psychologist who met regularly to define irritability and problem behavior, and then to review the evidence base on assessing and treating factors that contribute to irritability and problem behavior. They grouped these factors into five domains: “co-occurring medical conditions, lack of functional communication, psychosocial stressors, maladaptive reinforcement patterns, and co-occurring psychiatric conditions.”
Then the group developed a consensus in determining each step in the practice pathway and when it should occur, along with opportunities for a primary care provider to refer the patient to a specialist or to collaborate with school and community providers. The 10 steps in the practice pathway are:
1. Assess the patient for irritability and problem behavior based on the presence of tantrums, meltdowns or rages; property destruction; aggression toward others; and self-injury.
2. Assess the safety of the patient and others in the home, enlisting home-based crisis services or considering hospitalization if safety is threatened.
3. Review the patient’s medical, developmental, communication, environmental, and psychiatric history before and after the problem behavior. Include information on the caretaker’s characteristics, any loss of skills by patient, and any interference occurring with functioning or relationships.
4. Prioritize the behaviors to address based on safety, severity, and impact on daily life.
5. Consider all contributing factors to the problem behavior, including medical problems, difficulties functionally communicating, psychosocial stressors, maladaptive reinforcement patterns (reducing inadvertent triggers), and comorbid psychiatric disorders.
6. Consider possible medication treatments, such as N-acetylcysteine, clonidine, risperidone or aripiprazole, depending on circumstances.
7. Develop an individualized treatment and safety plan.
8. Implement and monitor the treatment plan, setting clear and measurable treatment goals.
9. Follow up at 3 months to assess whether symptoms are continuing and a reassessment is needed.
10. Reevaluate every 3 months.
The article provides a useful and extensive checklist with a variety of specific things to consider when implementing the 10 steps.
“No other provider in the patient’s life combines the medical expertise and first-hand knowledge of the individual patient’s health and development” than the primary care provider, the authors wrote. “The practice pathway is most likely to be efficient and effective in generating a treatment plan if it is systematically followed and the specific combination of individual contributing factors is identified for each patient.”
The research was conducted through the Autism Speaks Autism Treatment Network and funded by the U.S. Department of Health and Human Services with the Autism Intervention Research Network on Physical Health and by Marilyn and James Simons Family Giving. Dr. Jeremy Veenstra-VanderWeele has received research funding from Seaside Therapeutics, Roche, Novartis, Forest, Sunovion, and SynapDx and has consulted with Roche, Novartis and SynapDx.
A new practice pathway provides primary care providers with evidence-based steps in assessing and addressing irritability and problem behavior in patients at least 3 years old who have been diagnosed with an autism spectrum disorder (ASD).
“As the medical professionals whom children with ASD will probably encounter first and most frequently, pediatric primary care providers need a breadth of knowledge to enable them to identify contributing factors to irritability and problem behavior, decide when and how to initiate treatment, and judge when to refer to specialists,” reported Dr. Kelly McGuire of Columbia University Medical Center and New York State Psychiatric Institute, and her associates (Pediatrics. 2016 Feb;137 Suppl 2:S136-48). “Therefore, this practice pathway can be viewed more as a comprehensive rather than an exhaustive recommendation for [primary care physicians], who must weigh their expertise and resources when addressing the range of issues that a child with ASD and irritability and problem behavior may present.”
The Irritability Workgroup comprised eight child psychiatrists, a developmental pediatrician, and a behavioral psychologist who met regularly to define irritability and problem behavior, and then to review the evidence base on assessing and treating factors that contribute to irritability and problem behavior. They grouped these factors into five domains: “co-occurring medical conditions, lack of functional communication, psychosocial stressors, maladaptive reinforcement patterns, and co-occurring psychiatric conditions.”
Then the group developed a consensus in determining each step in the practice pathway and when it should occur, along with opportunities for a primary care provider to refer the patient to a specialist or to collaborate with school and community providers. The 10 steps in the practice pathway are:
1. Assess the patient for irritability and problem behavior based on the presence of tantrums, meltdowns or rages; property destruction; aggression toward others; and self-injury.
2. Assess the safety of the patient and others in the home, enlisting home-based crisis services or considering hospitalization if safety is threatened.
3. Review the patient’s medical, developmental, communication, environmental, and psychiatric history before and after the problem behavior. Include information on the caretaker’s characteristics, any loss of skills by patient, and any interference occurring with functioning or relationships.
4. Prioritize the behaviors to address based on safety, severity, and impact on daily life.
5. Consider all contributing factors to the problem behavior, including medical problems, difficulties functionally communicating, psychosocial stressors, maladaptive reinforcement patterns (reducing inadvertent triggers), and comorbid psychiatric disorders.
6. Consider possible medication treatments, such as N-acetylcysteine, clonidine, risperidone or aripiprazole, depending on circumstances.
7. Develop an individualized treatment and safety plan.
8. Implement and monitor the treatment plan, setting clear and measurable treatment goals.
9. Follow up at 3 months to assess whether symptoms are continuing and a reassessment is needed.
10. Reevaluate every 3 months.
The article provides a useful and extensive checklist with a variety of specific things to consider when implementing the 10 steps.
“No other provider in the patient’s life combines the medical expertise and first-hand knowledge of the individual patient’s health and development” than the primary care provider, the authors wrote. “The practice pathway is most likely to be efficient and effective in generating a treatment plan if it is systematically followed and the specific combination of individual contributing factors is identified for each patient.”
The research was conducted through the Autism Speaks Autism Treatment Network and funded by the U.S. Department of Health and Human Services with the Autism Intervention Research Network on Physical Health and by Marilyn and James Simons Family Giving. Dr. Jeremy Veenstra-VanderWeele has received research funding from Seaside Therapeutics, Roche, Novartis, Forest, Sunovion, and SynapDx and has consulted with Roche, Novartis and SynapDx.
A new practice pathway provides primary care providers with evidence-based steps in assessing and addressing irritability and problem behavior in patients at least 3 years old who have been diagnosed with an autism spectrum disorder (ASD).
“As the medical professionals whom children with ASD will probably encounter first and most frequently, pediatric primary care providers need a breadth of knowledge to enable them to identify contributing factors to irritability and problem behavior, decide when and how to initiate treatment, and judge when to refer to specialists,” reported Dr. Kelly McGuire of Columbia University Medical Center and New York State Psychiatric Institute, and her associates (Pediatrics. 2016 Feb;137 Suppl 2:S136-48). “Therefore, this practice pathway can be viewed more as a comprehensive rather than an exhaustive recommendation for [primary care physicians], who must weigh their expertise and resources when addressing the range of issues that a child with ASD and irritability and problem behavior may present.”
The Irritability Workgroup comprised eight child psychiatrists, a developmental pediatrician, and a behavioral psychologist who met regularly to define irritability and problem behavior, and then to review the evidence base on assessing and treating factors that contribute to irritability and problem behavior. They grouped these factors into five domains: “co-occurring medical conditions, lack of functional communication, psychosocial stressors, maladaptive reinforcement patterns, and co-occurring psychiatric conditions.”
Then the group developed a consensus in determining each step in the practice pathway and when it should occur, along with opportunities for a primary care provider to refer the patient to a specialist or to collaborate with school and community providers. The 10 steps in the practice pathway are:
1. Assess the patient for irritability and problem behavior based on the presence of tantrums, meltdowns or rages; property destruction; aggression toward others; and self-injury.
2. Assess the safety of the patient and others in the home, enlisting home-based crisis services or considering hospitalization if safety is threatened.
3. Review the patient’s medical, developmental, communication, environmental, and psychiatric history before and after the problem behavior. Include information on the caretaker’s characteristics, any loss of skills by patient, and any interference occurring with functioning or relationships.
4. Prioritize the behaviors to address based on safety, severity, and impact on daily life.
5. Consider all contributing factors to the problem behavior, including medical problems, difficulties functionally communicating, psychosocial stressors, maladaptive reinforcement patterns (reducing inadvertent triggers), and comorbid psychiatric disorders.
6. Consider possible medication treatments, such as N-acetylcysteine, clonidine, risperidone or aripiprazole, depending on circumstances.
7. Develop an individualized treatment and safety plan.
8. Implement and monitor the treatment plan, setting clear and measurable treatment goals.
9. Follow up at 3 months to assess whether symptoms are continuing and a reassessment is needed.
10. Reevaluate every 3 months.
The article provides a useful and extensive checklist with a variety of specific things to consider when implementing the 10 steps.
“No other provider in the patient’s life combines the medical expertise and first-hand knowledge of the individual patient’s health and development” than the primary care provider, the authors wrote. “The practice pathway is most likely to be efficient and effective in generating a treatment plan if it is systematically followed and the specific combination of individual contributing factors is identified for each patient.”
The research was conducted through the Autism Speaks Autism Treatment Network and funded by the U.S. Department of Health and Human Services with the Autism Intervention Research Network on Physical Health and by Marilyn and James Simons Family Giving. Dr. Jeremy Veenstra-VanderWeele has received research funding from Seaside Therapeutics, Roche, Novartis, Forest, Sunovion, and SynapDx and has consulted with Roche, Novartis and SynapDx.
FROM PEDIATRICS
Key clinical point: A 10-step practice pathway helps primary care providers address irritability and problem behavior in children with ASD.
Major finding: Ten steps in the pathway include assessment of problems, identification of contributing factors, and formulation of a plan to address the underlying factors and the behavior.
Data source: The pathway is based on a consensus by a 10-member multidisciplinary work group charged with identifying available evidence on effective ways to assess and address irritability and problem behavior in children with ASD.
Disclosures: The research was conducted through the Autism Speaks Autism Treatment Network and funded by the U.S. Department of Health and Human Services with the Autism Intervention Research Network on Physical Health and by Marilyn and James Simons Family Giving. Dr. Jeremy Veenstra-VanderWeele has received research funding from Seaside Therapeutics, Roche, Novartis, Forest, Sunovion and SynapDx and has consulted with Roche, Novartis and SynapDx.
MRSA incidence decreased in children as clindamycin resistance increased
The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections has decreased in children in recent years, but resistance to clindamycin has increased over the same period, a study showed.
“The epidemic of skin and soft tissue infections and invasive MRSA led to modifications of antimicrobial prescribing practices for suspected S. aureus infections,” reported Dr. Deena E. Sutter of the San Antonio Military Medical Center in Fort Sam Houston, Tex., and her associates. “Over the study period, erythromycin susceptibility among methicillin-susceptible S. aureus (MSSA) remained stable, suggesting that declining clindamycin susceptibility is a result of an increase in inducible resistance.”
The steady decline in clindamycin susceptibility “may lead to some concern about the continued reliance on clindamycin for the empirical treatment of presumptive S. aureus infections, although it is probably premature to abandon this effective antibiotic choice,” they wrote (Pediatrics. 2016 Mar. 1. doi: 10.1542/peds.2015-3099). “It is crucial that clinicians remain knowledgeable about local susceptibility rates as it would be prudent to consider [alternative] antimicrobial agents for empirical use when the local clindamycin susceptibility rate drops below 85%.”
The researchers retrospectively analyzed lab results from 39,209 patients under age 18 who were treated for S. aureus infections at one of the 266 U.S. facilities of the Military Health System from 2005 to 2014. The data included 41,745 S. aureus isolates, classified as MRSA if found resistant to cefoxitin, methicillin, or oxacillin and as methicillin susceptible (MSSA) if susceptible to those antimicrobials. The isolates had also been tested for susceptibility to ciprofloxacin, clindamycin, erythromycin, gentamicin, oxacillin, penicillin, rifampin, tetracycline, and trimethoprim/sulfamethoxazole (TMP/SMX).
During that decade, overall S. aureus susceptibility to clindamycin, ciprofloxacin, and TMP/SMX decreased – although susceptibility to TMP/SMX in 2014 stayed high at 98% – while overall susceptibility to erythromycin, gentamicin, and oxacillin increased. Specifically, 59% of S. aureus isolates were susceptible to oxacillin in 2005, which dropped briefly to 54% in 2007 before climbing to the 2014 rate of 68%.
Meanwhile, overall susceptibility to clindamycin dropped from 91% in 2005 to 86% in 2014, and MSSA susceptibility to clindamycin dropped from 91% in 2005 to 84% in 2014. “Erythromycin susceptibility remained stable among MSSA isolates throughout the study period at 63.5%, whereas MRSA susceptibility to erythromycin increased from 12.1% to 20.5%,” Dr. Sutter and her associates reported. “Ciprofloxacin susceptibility significantly decreased overall, although an initial decrease of 10.6% over the first 7 years of the study was subsequently followed by an increase of 6% between 2011 and 2014.”
Most of the isolates came from patients with skin and soft tissue infections, which were less likely to be susceptible to oxacillin than were other infections. Infections in children aged 1-5 years also were less likely to be susceptible to oxacillin, compared with infections in children of other age groups.
If the local clindamycin susceptibility rate falls below 85%, “beta-lactams, TMP/SMX, or tetracyclines may be used for less severe infections with intravenous vancomycin employed in severe cases,” the investigators said. “If overall MRSA rates continue to decline and clindamycin resistance among MSSA continues to increase, we may see a return to antistaphylococcal beta-lactam antimicrobial agents such as oxacillin or first-generation cephalosporins as preferred empirical therapy for presumed S. aureus infections.”
The research did not use external funding, and the authors reported no relevant financial disclosures.
Staphylococcus aureus is one of the most common organisms isolated from children with health care–associated infections, regardless of whether these infections had their onset in the community or were acquired in the hospital. Thus, the initial empiric treatment of a skin or soft tissue infection or invasive infection in a child almost always includes an antibiotic effective against S. aureus.
However, over the years, clindamycin susceptibility among S. aureus isolates has declined, likely related to the increased use of this agent for empiric as well as definitive treatment of community-acquired (CA) MRSA infections, encouraging the transmission of the genes associated with clindamycin resistance.
What are the implications of the findings from the report by Sutter et al. with respect to the selection of empiric antibiotics for children with suspected S. aureus infections? Currently, considering the still substantial MRSA resistance rates that exceed the 10%-15% level suggested by many experts as the threshold above which agents effective against CA-MRSA isolates should be administered for empiric treatment, changes in the selection of empiric antibiotics are not warranted. If rates of MRSA among S. aureus isolates from otherwise normal children are documented to drop below the 10%-15% threshold in different communities, a modification of current recommendations should be considered. It would also be important to understand why methicillin resistance is declining among S. aureus isolates from CA infections; this information may provide clues for preventing CA-MRSA infections with the use of vaccines or other means. The epidemiology of S. aureus infections in children has been changing over the past 2 decades, which is why it is critical to keep a very close eye on this common pathogen.
These comments were excerpted from an accompanying commentary by Dr. Sheldon L. Kaplan of the infectious disease service at Texas Children’s Hospital in Houston (Pediatrics. 2016 Mar 1. doi: 10.1542/peds.2016-0101). Dr. Kaplan has received research funds from Pfizer, Forest Laboratories, and Cubist.
Staphylococcus aureus is one of the most common organisms isolated from children with health care–associated infections, regardless of whether these infections had their onset in the community or were acquired in the hospital. Thus, the initial empiric treatment of a skin or soft tissue infection or invasive infection in a child almost always includes an antibiotic effective against S. aureus.
However, over the years, clindamycin susceptibility among S. aureus isolates has declined, likely related to the increased use of this agent for empiric as well as definitive treatment of community-acquired (CA) MRSA infections, encouraging the transmission of the genes associated with clindamycin resistance.
What are the implications of the findings from the report by Sutter et al. with respect to the selection of empiric antibiotics for children with suspected S. aureus infections? Currently, considering the still substantial MRSA resistance rates that exceed the 10%-15% level suggested by many experts as the threshold above which agents effective against CA-MRSA isolates should be administered for empiric treatment, changes in the selection of empiric antibiotics are not warranted. If rates of MRSA among S. aureus isolates from otherwise normal children are documented to drop below the 10%-15% threshold in different communities, a modification of current recommendations should be considered. It would also be important to understand why methicillin resistance is declining among S. aureus isolates from CA infections; this information may provide clues for preventing CA-MRSA infections with the use of vaccines or other means. The epidemiology of S. aureus infections in children has been changing over the past 2 decades, which is why it is critical to keep a very close eye on this common pathogen.
These comments were excerpted from an accompanying commentary by Dr. Sheldon L. Kaplan of the infectious disease service at Texas Children’s Hospital in Houston (Pediatrics. 2016 Mar 1. doi: 10.1542/peds.2016-0101). Dr. Kaplan has received research funds from Pfizer, Forest Laboratories, and Cubist.
Staphylococcus aureus is one of the most common organisms isolated from children with health care–associated infections, regardless of whether these infections had their onset in the community or were acquired in the hospital. Thus, the initial empiric treatment of a skin or soft tissue infection or invasive infection in a child almost always includes an antibiotic effective against S. aureus.
However, over the years, clindamycin susceptibility among S. aureus isolates has declined, likely related to the increased use of this agent for empiric as well as definitive treatment of community-acquired (CA) MRSA infections, encouraging the transmission of the genes associated with clindamycin resistance.
What are the implications of the findings from the report by Sutter et al. with respect to the selection of empiric antibiotics for children with suspected S. aureus infections? Currently, considering the still substantial MRSA resistance rates that exceed the 10%-15% level suggested by many experts as the threshold above which agents effective against CA-MRSA isolates should be administered for empiric treatment, changes in the selection of empiric antibiotics are not warranted. If rates of MRSA among S. aureus isolates from otherwise normal children are documented to drop below the 10%-15% threshold in different communities, a modification of current recommendations should be considered. It would also be important to understand why methicillin resistance is declining among S. aureus isolates from CA infections; this information may provide clues for preventing CA-MRSA infections with the use of vaccines or other means. The epidemiology of S. aureus infections in children has been changing over the past 2 decades, which is why it is critical to keep a very close eye on this common pathogen.
These comments were excerpted from an accompanying commentary by Dr. Sheldon L. Kaplan of the infectious disease service at Texas Children’s Hospital in Houston (Pediatrics. 2016 Mar 1. doi: 10.1542/peds.2016-0101). Dr. Kaplan has received research funds from Pfizer, Forest Laboratories, and Cubist.
The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections has decreased in children in recent years, but resistance to clindamycin has increased over the same period, a study showed.
“The epidemic of skin and soft tissue infections and invasive MRSA led to modifications of antimicrobial prescribing practices for suspected S. aureus infections,” reported Dr. Deena E. Sutter of the San Antonio Military Medical Center in Fort Sam Houston, Tex., and her associates. “Over the study period, erythromycin susceptibility among methicillin-susceptible S. aureus (MSSA) remained stable, suggesting that declining clindamycin susceptibility is a result of an increase in inducible resistance.”
The steady decline in clindamycin susceptibility “may lead to some concern about the continued reliance on clindamycin for the empirical treatment of presumptive S. aureus infections, although it is probably premature to abandon this effective antibiotic choice,” they wrote (Pediatrics. 2016 Mar. 1. doi: 10.1542/peds.2015-3099). “It is crucial that clinicians remain knowledgeable about local susceptibility rates as it would be prudent to consider [alternative] antimicrobial agents for empirical use when the local clindamycin susceptibility rate drops below 85%.”
The researchers retrospectively analyzed lab results from 39,209 patients under age 18 who were treated for S. aureus infections at one of the 266 U.S. facilities of the Military Health System from 2005 to 2014. The data included 41,745 S. aureus isolates, classified as MRSA if found resistant to cefoxitin, methicillin, or oxacillin and as methicillin susceptible (MSSA) if susceptible to those antimicrobials. The isolates had also been tested for susceptibility to ciprofloxacin, clindamycin, erythromycin, gentamicin, oxacillin, penicillin, rifampin, tetracycline, and trimethoprim/sulfamethoxazole (TMP/SMX).
During that decade, overall S. aureus susceptibility to clindamycin, ciprofloxacin, and TMP/SMX decreased – although susceptibility to TMP/SMX in 2014 stayed high at 98% – while overall susceptibility to erythromycin, gentamicin, and oxacillin increased. Specifically, 59% of S. aureus isolates were susceptible to oxacillin in 2005, which dropped briefly to 54% in 2007 before climbing to the 2014 rate of 68%.
Meanwhile, overall susceptibility to clindamycin dropped from 91% in 2005 to 86% in 2014, and MSSA susceptibility to clindamycin dropped from 91% in 2005 to 84% in 2014. “Erythromycin susceptibility remained stable among MSSA isolates throughout the study period at 63.5%, whereas MRSA susceptibility to erythromycin increased from 12.1% to 20.5%,” Dr. Sutter and her associates reported. “Ciprofloxacin susceptibility significantly decreased overall, although an initial decrease of 10.6% over the first 7 years of the study was subsequently followed by an increase of 6% between 2011 and 2014.”
Most of the isolates came from patients with skin and soft tissue infections, which were less likely to be susceptible to oxacillin than were other infections. Infections in children aged 1-5 years also were less likely to be susceptible to oxacillin, compared with infections in children of other age groups.
If the local clindamycin susceptibility rate falls below 85%, “beta-lactams, TMP/SMX, or tetracyclines may be used for less severe infections with intravenous vancomycin employed in severe cases,” the investigators said. “If overall MRSA rates continue to decline and clindamycin resistance among MSSA continues to increase, we may see a return to antistaphylococcal beta-lactam antimicrobial agents such as oxacillin or first-generation cephalosporins as preferred empirical therapy for presumed S. aureus infections.”
The research did not use external funding, and the authors reported no relevant financial disclosures.
The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections has decreased in children in recent years, but resistance to clindamycin has increased over the same period, a study showed.
“The epidemic of skin and soft tissue infections and invasive MRSA led to modifications of antimicrobial prescribing practices for suspected S. aureus infections,” reported Dr. Deena E. Sutter of the San Antonio Military Medical Center in Fort Sam Houston, Tex., and her associates. “Over the study period, erythromycin susceptibility among methicillin-susceptible S. aureus (MSSA) remained stable, suggesting that declining clindamycin susceptibility is a result of an increase in inducible resistance.”
The steady decline in clindamycin susceptibility “may lead to some concern about the continued reliance on clindamycin for the empirical treatment of presumptive S. aureus infections, although it is probably premature to abandon this effective antibiotic choice,” they wrote (Pediatrics. 2016 Mar. 1. doi: 10.1542/peds.2015-3099). “It is crucial that clinicians remain knowledgeable about local susceptibility rates as it would be prudent to consider [alternative] antimicrobial agents for empirical use when the local clindamycin susceptibility rate drops below 85%.”
The researchers retrospectively analyzed lab results from 39,209 patients under age 18 who were treated for S. aureus infections at one of the 266 U.S. facilities of the Military Health System from 2005 to 2014. The data included 41,745 S. aureus isolates, classified as MRSA if found resistant to cefoxitin, methicillin, or oxacillin and as methicillin susceptible (MSSA) if susceptible to those antimicrobials. The isolates had also been tested for susceptibility to ciprofloxacin, clindamycin, erythromycin, gentamicin, oxacillin, penicillin, rifampin, tetracycline, and trimethoprim/sulfamethoxazole (TMP/SMX).
During that decade, overall S. aureus susceptibility to clindamycin, ciprofloxacin, and TMP/SMX decreased – although susceptibility to TMP/SMX in 2014 stayed high at 98% – while overall susceptibility to erythromycin, gentamicin, and oxacillin increased. Specifically, 59% of S. aureus isolates were susceptible to oxacillin in 2005, which dropped briefly to 54% in 2007 before climbing to the 2014 rate of 68%.
Meanwhile, overall susceptibility to clindamycin dropped from 91% in 2005 to 86% in 2014, and MSSA susceptibility to clindamycin dropped from 91% in 2005 to 84% in 2014. “Erythromycin susceptibility remained stable among MSSA isolates throughout the study period at 63.5%, whereas MRSA susceptibility to erythromycin increased from 12.1% to 20.5%,” Dr. Sutter and her associates reported. “Ciprofloxacin susceptibility significantly decreased overall, although an initial decrease of 10.6% over the first 7 years of the study was subsequently followed by an increase of 6% between 2011 and 2014.”
Most of the isolates came from patients with skin and soft tissue infections, which were less likely to be susceptible to oxacillin than were other infections. Infections in children aged 1-5 years also were less likely to be susceptible to oxacillin, compared with infections in children of other age groups.
If the local clindamycin susceptibility rate falls below 85%, “beta-lactams, TMP/SMX, or tetracyclines may be used for less severe infections with intravenous vancomycin employed in severe cases,” the investigators said. “If overall MRSA rates continue to decline and clindamycin resistance among MSSA continues to increase, we may see a return to antistaphylococcal beta-lactam antimicrobial agents such as oxacillin or first-generation cephalosporins as preferred empirical therapy for presumed S. aureus infections.”
The research did not use external funding, and the authors reported no relevant financial disclosures.
FROM PEDIATRICS
Key clinical point: The incidence of methicillin-resistant Staphylococcus aureus infections has decreased in children in recent years while resistance to clindamycin has increased.
Major finding: MRSA susceptibility to oxacillin increased to 68.4% in 2014, and susceptibility dropped to 86% for clindamycin.
Data source: A retrospective analysis of 41,745 S. aureus isolates from 39,209 patients under age 18 years in the U.S. Military Health System between 2005 and 2014.
Disclosures: The research did not use external funding, and the authors reported no relevant financial disclosures.
Uveitis in juvenile idiopathic arthritis may be preventable
MAUI, HAWAII – Uveitis is a common, highly destructive manifestation of juvenile idiopathic arthritis that is readily treatable when caught early, Dr. Anne M. Stevens said at the 2016 Rheumatology Winter Clinical Symposium.
Moreover, recent evidence from Germany suggests that uveitis may actually be preventable through early aggressive anti-inflammatory therapy, noted Dr. Stevens, a pediatric rheumatologist at Seattle Children’s Hospital and the University of Washington.
She cited a report from investigators participating in the National Pediatric Rheumatological Database in Germany. This large study included 3,512 juvenile idiopathic arthritis (JIA) patients with a mean age at arthritis onset of 7.8 years, a disease duration of less than 12 months at enrollment, and a mean follow-up of 3.6 years.
Uveitis occurred in 5.1% of patients within the first year after onset of JIA, and in another 7.1% following the first year. The key finding in the German study was that aggressive disease-modifying antirheumatic drug (DMARD) therapy during the year prior to uveitis significantly reduced the likelihood of developing this complication. Children on methotrexate during that time period were 37% less likely to develop uveitis than were those not on a DMARD. Moreover, patients placed on methotrexate within the first year after being diagnosed with JIA had a 71% relative risk reduction.
Patients on a tumor necrosis factor inhibitor during the year prior to uveitis had a 44% reduction in the risk of developing the eye complication. Most impressive of all, children on both methotrexate and a TNF inhibitor during the year prior to uveitis had a whopping 90% reduction in the risk of developing uveitis, compared with those not on a DMARD (Arthritis Care Res [Hoboken]. 2016 Jan;68[1]:46-54).
“I was fascinated by this study showing that treatment with two types of therapy may be preventive,” Dr. Stevens commented. “If this is substantiated in another large population-based cohort, it will be interesting to see if practice moves to treating the ANA [antinuclear antibody]–positive oligo JIA patients very early with TNF [tumor necrosis factor] inhibitors and methotrexate to prevent uveitis.”
The logic behind this aggressive preventive therapy lies in the fact that while uveitis occurs in about 20% of patients with oligoarticular JIA overall, roughly 90% of cases involve ANA-positive patients. For this reason, guidelines recommend slit lamp examinations every 3 months for a year in patients with young-onset, ANA-positive JIA.
“Imagine trying to do a slit lamp exam on a 2-year-old. It really helps to send these kids to a pediatric ophthalmologist who’s done a lot of them,” she advised.
The uveitis of JIA is typically anterior, asymptomatic, and low grade. It’s also a leading cause of blindness in childhood. Complications include band keratopathy, glaucomatous optic neuropathy, cataracts, and maculopathy.
“If we catch uveitis early, we can treat this disease really well now,” according to Dr. Stevens.
The initial therapy is short-term topical steroids. It’s important to keep in touch with the ophthalmologist regarding the slit lamp findings, however, because ophthalmologists generally tend to favor longer-term topical steroid therapy, while rheumatologists are appropriately primed to push on to more aggressive systemic therapy very quickly.
The first-line systemic agent for treatment of uveitis in patients with JIA is methotrexate at 1 mg/kg/week. If that doesn’t achieve satisfactory results, pediatric rheumatologists are quick to move on to second-line therapy with cyclosporine, azathioprine, or mycophenolate (CellCept).
“We move on fairly quickly if need be to TNF inhibitors, and we go with very high doses. The literature for infliximab [Remicade] is supportive of 20 mg/kg every 4 weeks. That’s what I use,” she continued.
High-dose adalimumab (Humira) is another option (J Rheumatol. 2013 Jan;40[1]:74-9). However, etanercept (Enbrel) is not effective for this condition. The use of abatacept (Orencia) or rituximab (Rituxan) in refractory patients is supported by favorable case reports.
Dr. Stevens reported having no financial interests relevant to her presentation.
MAUI, HAWAII – Uveitis is a common, highly destructive manifestation of juvenile idiopathic arthritis that is readily treatable when caught early, Dr. Anne M. Stevens said at the 2016 Rheumatology Winter Clinical Symposium.
Moreover, recent evidence from Germany suggests that uveitis may actually be preventable through early aggressive anti-inflammatory therapy, noted Dr. Stevens, a pediatric rheumatologist at Seattle Children’s Hospital and the University of Washington.
She cited a report from investigators participating in the National Pediatric Rheumatological Database in Germany. This large study included 3,512 juvenile idiopathic arthritis (JIA) patients with a mean age at arthritis onset of 7.8 years, a disease duration of less than 12 months at enrollment, and a mean follow-up of 3.6 years.
Uveitis occurred in 5.1% of patients within the first year after onset of JIA, and in another 7.1% following the first year. The key finding in the German study was that aggressive disease-modifying antirheumatic drug (DMARD) therapy during the year prior to uveitis significantly reduced the likelihood of developing this complication. Children on methotrexate during that time period were 37% less likely to develop uveitis than were those not on a DMARD. Moreover, patients placed on methotrexate within the first year after being diagnosed with JIA had a 71% relative risk reduction.
Patients on a tumor necrosis factor inhibitor during the year prior to uveitis had a 44% reduction in the risk of developing the eye complication. Most impressive of all, children on both methotrexate and a TNF inhibitor during the year prior to uveitis had a whopping 90% reduction in the risk of developing uveitis, compared with those not on a DMARD (Arthritis Care Res [Hoboken]. 2016 Jan;68[1]:46-54).
“I was fascinated by this study showing that treatment with two types of therapy may be preventive,” Dr. Stevens commented. “If this is substantiated in another large population-based cohort, it will be interesting to see if practice moves to treating the ANA [antinuclear antibody]–positive oligo JIA patients very early with TNF [tumor necrosis factor] inhibitors and methotrexate to prevent uveitis.”
The logic behind this aggressive preventive therapy lies in the fact that while uveitis occurs in about 20% of patients with oligoarticular JIA overall, roughly 90% of cases involve ANA-positive patients. For this reason, guidelines recommend slit lamp examinations every 3 months for a year in patients with young-onset, ANA-positive JIA.
“Imagine trying to do a slit lamp exam on a 2-year-old. It really helps to send these kids to a pediatric ophthalmologist who’s done a lot of them,” she advised.
The uveitis of JIA is typically anterior, asymptomatic, and low grade. It’s also a leading cause of blindness in childhood. Complications include band keratopathy, glaucomatous optic neuropathy, cataracts, and maculopathy.
“If we catch uveitis early, we can treat this disease really well now,” according to Dr. Stevens.
The initial therapy is short-term topical steroids. It’s important to keep in touch with the ophthalmologist regarding the slit lamp findings, however, because ophthalmologists generally tend to favor longer-term topical steroid therapy, while rheumatologists are appropriately primed to push on to more aggressive systemic therapy very quickly.
The first-line systemic agent for treatment of uveitis in patients with JIA is methotrexate at 1 mg/kg/week. If that doesn’t achieve satisfactory results, pediatric rheumatologists are quick to move on to second-line therapy with cyclosporine, azathioprine, or mycophenolate (CellCept).
“We move on fairly quickly if need be to TNF inhibitors, and we go with very high doses. The literature for infliximab [Remicade] is supportive of 20 mg/kg every 4 weeks. That’s what I use,” she continued.
High-dose adalimumab (Humira) is another option (J Rheumatol. 2013 Jan;40[1]:74-9). However, etanercept (Enbrel) is not effective for this condition. The use of abatacept (Orencia) or rituximab (Rituxan) in refractory patients is supported by favorable case reports.
Dr. Stevens reported having no financial interests relevant to her presentation.
MAUI, HAWAII – Uveitis is a common, highly destructive manifestation of juvenile idiopathic arthritis that is readily treatable when caught early, Dr. Anne M. Stevens said at the 2016 Rheumatology Winter Clinical Symposium.
Moreover, recent evidence from Germany suggests that uveitis may actually be preventable through early aggressive anti-inflammatory therapy, noted Dr. Stevens, a pediatric rheumatologist at Seattle Children’s Hospital and the University of Washington.
She cited a report from investigators participating in the National Pediatric Rheumatological Database in Germany. This large study included 3,512 juvenile idiopathic arthritis (JIA) patients with a mean age at arthritis onset of 7.8 years, a disease duration of less than 12 months at enrollment, and a mean follow-up of 3.6 years.
Uveitis occurred in 5.1% of patients within the first year after onset of JIA, and in another 7.1% following the first year. The key finding in the German study was that aggressive disease-modifying antirheumatic drug (DMARD) therapy during the year prior to uveitis significantly reduced the likelihood of developing this complication. Children on methotrexate during that time period were 37% less likely to develop uveitis than were those not on a DMARD. Moreover, patients placed on methotrexate within the first year after being diagnosed with JIA had a 71% relative risk reduction.
Patients on a tumor necrosis factor inhibitor during the year prior to uveitis had a 44% reduction in the risk of developing the eye complication. Most impressive of all, children on both methotrexate and a TNF inhibitor during the year prior to uveitis had a whopping 90% reduction in the risk of developing uveitis, compared with those not on a DMARD (Arthritis Care Res [Hoboken]. 2016 Jan;68[1]:46-54).
“I was fascinated by this study showing that treatment with two types of therapy may be preventive,” Dr. Stevens commented. “If this is substantiated in another large population-based cohort, it will be interesting to see if practice moves to treating the ANA [antinuclear antibody]–positive oligo JIA patients very early with TNF [tumor necrosis factor] inhibitors and methotrexate to prevent uveitis.”
The logic behind this aggressive preventive therapy lies in the fact that while uveitis occurs in about 20% of patients with oligoarticular JIA overall, roughly 90% of cases involve ANA-positive patients. For this reason, guidelines recommend slit lamp examinations every 3 months for a year in patients with young-onset, ANA-positive JIA.
“Imagine trying to do a slit lamp exam on a 2-year-old. It really helps to send these kids to a pediatric ophthalmologist who’s done a lot of them,” she advised.
The uveitis of JIA is typically anterior, asymptomatic, and low grade. It’s also a leading cause of blindness in childhood. Complications include band keratopathy, glaucomatous optic neuropathy, cataracts, and maculopathy.
“If we catch uveitis early, we can treat this disease really well now,” according to Dr. Stevens.
The initial therapy is short-term topical steroids. It’s important to keep in touch with the ophthalmologist regarding the slit lamp findings, however, because ophthalmologists generally tend to favor longer-term topical steroid therapy, while rheumatologists are appropriately primed to push on to more aggressive systemic therapy very quickly.
The first-line systemic agent for treatment of uveitis in patients with JIA is methotrexate at 1 mg/kg/week. If that doesn’t achieve satisfactory results, pediatric rheumatologists are quick to move on to second-line therapy with cyclosporine, azathioprine, or mycophenolate (CellCept).
“We move on fairly quickly if need be to TNF inhibitors, and we go with very high doses. The literature for infliximab [Remicade] is supportive of 20 mg/kg every 4 weeks. That’s what I use,” she continued.
High-dose adalimumab (Humira) is another option (J Rheumatol. 2013 Jan;40[1]:74-9). However, etanercept (Enbrel) is not effective for this condition. The use of abatacept (Orencia) or rituximab (Rituxan) in refractory patients is supported by favorable case reports.
Dr. Stevens reported having no financial interests relevant to her presentation.
EXPERT ANALYSIS FROM RWCS 2016
Childhood Emotional Abuse Fuels Odds for Migraine in Adulthood
Emotionally abused children are 52% more likely to develop migraine in young adulthood than are those who were never abused, based on longitudinal survey data from nearly 15,000 individuals.
“Childhood maltreatment, and especially emotional abuse, is a common, likely under-recognized occurrence, which has enduring consequences for health throughout life. The association of emotional abuse with migraine has not heretofore been well studied, being the subject of only population-based study,” lead author Dr. Gretchen E. Tietjen of the University of Toledo (Ohio) said in an interview in advance of the presentation of the study at the annual meeting of the American Academy of Neurology in Vancouver in April.
Dr. Tietjen and her colleagues assessed data from 14,484 adults aged 24-32 years who took part in wave four of the National Longitudinal Study of Adolescent to Adult Health. Of these, 2,061 (14%) reported a migraine diagnosis, and 1,246 (60%) of those diagnosed with migraines reported some type of childhood abuse. A total of 6,088 (49%) individuals without migraine reported some type of childhood abuse.
Overall, the odds of migraine in adulthood was 55% higher in children who reported emotional abuse, physical abuse, or sexual abuse, compared with those who reported no childhood abuse, after controlling for age, race, sex, and income (odds ratio, 1.55; 95% confidence interval, 1.35-1.77). However, only emotional abuse remained significantly associated with increased odds for migraine after controlling for other types of abuse (OR, 1.52; 95% CI, 1.34-1.73).
Emotional abuse was assessed by asking, “How often did a parent or other adult caregiver say things that really hurt your feelings or made you feel like you were not wanted or loved?” Physical abuse was defined as being hit with a fist, kicked, or thrown down on the floor, into a wall, or down stairs. Sexual abuse included forced sexual touching or sexual relations.
Controlling for depression and anxiety weakened the associations between childhood abuse overall and likelihood of migraine in young adulthood, as well as for emotional abuse in particular, but the relationships remained statistically significant (OR, 1.32 and 1.33, respectively).
Dr. Tietjen said she was surprised by the absence of an association between migraine and physical and sexual abuse after controlling for other types of abuse.
“Sexual and physical abuse may be less frequent, occur over a briefer duration, and if limited, lead in some cases to resilience,” Dr. Tietjen noted. “Emotional abuse is likely more insidious, being ingrained in the fabric of the family dynamic. It may occur over years without recognition or intervention,” she said. “This type of abuse may cause more cumulative stress, with subsequent dysregulation of the HPA axis, immune, autonomic, and metabolic systems,” she added.
The study does not show cause and effect, the researchers noted, and more research is needed. But the findings suggest that clinicians might consider childhood abuse when counseling adult migraine patients.
“In migraineurs, childhood abuse, particularly emotional abuse, is common and possibly causally related,” Dr. Tietjen said. “Knowledge of adverse childhood experiences allows physicians to identify migraineurs at higher risk for psychiatric disease, pain comorbidities, and conditions associated with inflammation. These patients would likely benefit from exposure to cognitive behavioral therapy strategies, in order to decrease neurophysiological responses to stress,” she noted.
“There are currently therapies which reverse stress-induced epigenetic changes, which might be particularly useful in the subset of migraineurs who have been abused,” said Dr. Tietjen. Her next steps for research involve studying the effect of early life stress on factors such as pain sensitivity, anxiety, and depression.
The University of Toledo and the Clair Martig Endowment funded the study.
Emotionally abused children are 52% more likely to develop migraine in young adulthood than are those who were never abused, based on longitudinal survey data from nearly 15,000 individuals.
“Childhood maltreatment, and especially emotional abuse, is a common, likely under-recognized occurrence, which has enduring consequences for health throughout life. The association of emotional abuse with migraine has not heretofore been well studied, being the subject of only population-based study,” lead author Dr. Gretchen E. Tietjen of the University of Toledo (Ohio) said in an interview in advance of the presentation of the study at the annual meeting of the American Academy of Neurology in Vancouver in April.
Dr. Tietjen and her colleagues assessed data from 14,484 adults aged 24-32 years who took part in wave four of the National Longitudinal Study of Adolescent to Adult Health. Of these, 2,061 (14%) reported a migraine diagnosis, and 1,246 (60%) of those diagnosed with migraines reported some type of childhood abuse. A total of 6,088 (49%) individuals without migraine reported some type of childhood abuse.
Overall, the odds of migraine in adulthood was 55% higher in children who reported emotional abuse, physical abuse, or sexual abuse, compared with those who reported no childhood abuse, after controlling for age, race, sex, and income (odds ratio, 1.55; 95% confidence interval, 1.35-1.77). However, only emotional abuse remained significantly associated with increased odds for migraine after controlling for other types of abuse (OR, 1.52; 95% CI, 1.34-1.73).
Emotional abuse was assessed by asking, “How often did a parent or other adult caregiver say things that really hurt your feelings or made you feel like you were not wanted or loved?” Physical abuse was defined as being hit with a fist, kicked, or thrown down on the floor, into a wall, or down stairs. Sexual abuse included forced sexual touching or sexual relations.
Controlling for depression and anxiety weakened the associations between childhood abuse overall and likelihood of migraine in young adulthood, as well as for emotional abuse in particular, but the relationships remained statistically significant (OR, 1.32 and 1.33, respectively).
Dr. Tietjen said she was surprised by the absence of an association between migraine and physical and sexual abuse after controlling for other types of abuse.
“Sexual and physical abuse may be less frequent, occur over a briefer duration, and if limited, lead in some cases to resilience,” Dr. Tietjen noted. “Emotional abuse is likely more insidious, being ingrained in the fabric of the family dynamic. It may occur over years without recognition or intervention,” she said. “This type of abuse may cause more cumulative stress, with subsequent dysregulation of the HPA axis, immune, autonomic, and metabolic systems,” she added.
The study does not show cause and effect, the researchers noted, and more research is needed. But the findings suggest that clinicians might consider childhood abuse when counseling adult migraine patients.
“In migraineurs, childhood abuse, particularly emotional abuse, is common and possibly causally related,” Dr. Tietjen said. “Knowledge of adverse childhood experiences allows physicians to identify migraineurs at higher risk for psychiatric disease, pain comorbidities, and conditions associated with inflammation. These patients would likely benefit from exposure to cognitive behavioral therapy strategies, in order to decrease neurophysiological responses to stress,” she noted.
“There are currently therapies which reverse stress-induced epigenetic changes, which might be particularly useful in the subset of migraineurs who have been abused,” said Dr. Tietjen. Her next steps for research involve studying the effect of early life stress on factors such as pain sensitivity, anxiety, and depression.
The University of Toledo and the Clair Martig Endowment funded the study.
Emotionally abused children are 52% more likely to develop migraine in young adulthood than are those who were never abused, based on longitudinal survey data from nearly 15,000 individuals.
“Childhood maltreatment, and especially emotional abuse, is a common, likely under-recognized occurrence, which has enduring consequences for health throughout life. The association of emotional abuse with migraine has not heretofore been well studied, being the subject of only population-based study,” lead author Dr. Gretchen E. Tietjen of the University of Toledo (Ohio) said in an interview in advance of the presentation of the study at the annual meeting of the American Academy of Neurology in Vancouver in April.
Dr. Tietjen and her colleagues assessed data from 14,484 adults aged 24-32 years who took part in wave four of the National Longitudinal Study of Adolescent to Adult Health. Of these, 2,061 (14%) reported a migraine diagnosis, and 1,246 (60%) of those diagnosed with migraines reported some type of childhood abuse. A total of 6,088 (49%) individuals without migraine reported some type of childhood abuse.
Overall, the odds of migraine in adulthood was 55% higher in children who reported emotional abuse, physical abuse, or sexual abuse, compared with those who reported no childhood abuse, after controlling for age, race, sex, and income (odds ratio, 1.55; 95% confidence interval, 1.35-1.77). However, only emotional abuse remained significantly associated with increased odds for migraine after controlling for other types of abuse (OR, 1.52; 95% CI, 1.34-1.73).
Emotional abuse was assessed by asking, “How often did a parent or other adult caregiver say things that really hurt your feelings or made you feel like you were not wanted or loved?” Physical abuse was defined as being hit with a fist, kicked, or thrown down on the floor, into a wall, or down stairs. Sexual abuse included forced sexual touching or sexual relations.
Controlling for depression and anxiety weakened the associations between childhood abuse overall and likelihood of migraine in young adulthood, as well as for emotional abuse in particular, but the relationships remained statistically significant (OR, 1.32 and 1.33, respectively).
Dr. Tietjen said she was surprised by the absence of an association between migraine and physical and sexual abuse after controlling for other types of abuse.
“Sexual and physical abuse may be less frequent, occur over a briefer duration, and if limited, lead in some cases to resilience,” Dr. Tietjen noted. “Emotional abuse is likely more insidious, being ingrained in the fabric of the family dynamic. It may occur over years without recognition or intervention,” she said. “This type of abuse may cause more cumulative stress, with subsequent dysregulation of the HPA axis, immune, autonomic, and metabolic systems,” she added.
The study does not show cause and effect, the researchers noted, and more research is needed. But the findings suggest that clinicians might consider childhood abuse when counseling adult migraine patients.
“In migraineurs, childhood abuse, particularly emotional abuse, is common and possibly causally related,” Dr. Tietjen said. “Knowledge of adverse childhood experiences allows physicians to identify migraineurs at higher risk for psychiatric disease, pain comorbidities, and conditions associated with inflammation. These patients would likely benefit from exposure to cognitive behavioral therapy strategies, in order to decrease neurophysiological responses to stress,” she noted.
“There are currently therapies which reverse stress-induced epigenetic changes, which might be particularly useful in the subset of migraineurs who have been abused,” said Dr. Tietjen. Her next steps for research involve studying the effect of early life stress on factors such as pain sensitivity, anxiety, and depression.
The University of Toledo and the Clair Martig Endowment funded the study.
FROM THE AAN 2016 ANNUAL MEETING
Childhood emotional abuse fuels odds for migraine in adulthood
Emotionally abused children are 52% more likely to develop migraine in young adulthood than are those who were never abused, based on longitudinal survey data from nearly 15,000 individuals.
“Childhood maltreatment, and especially emotional abuse, is a common, likely under-recognized occurrence, which has enduring consequences for health throughout life. The association of emotional abuse with migraine has not heretofore been well studied, being the subject of only population-based study,” lead author Dr. Gretchen E. Tietjen of the University of Toledo (Ohio) said in an interview in advance of the presentation of the study at the annual meeting of the American Academy of Neurology in Vancouver in April.
Dr. Tietjen and her colleagues assessed data from 14,484 adults aged 24-32 years who took part in wave four of the National Longitudinal Study of Adolescent to Adult Health. Of these, 2,061 (14%) reported a migraine diagnosis, and 1,246 (60%) of those diagnosed with migraines reported some type of childhood abuse. A total of 6,088 (49%) individuals without migraine reported some type of childhood abuse.
Overall, the odds of migraine in adulthood was 55% higher in children who reported emotional abuse, physical abuse, or sexual abuse, compared with those who reported no childhood abuse, after controlling for age, race, sex, and income (odds ratio, 1.55; 95% confidence interval, 1.35-1.77). However, only emotional abuse remained significantly associated with increased odds for migraine after controlling for other types of abuse (OR, 1.52; 95% CI, 1.34-1.73).
Emotional abuse was assessed by asking, “How often did a parent or other adult caregiver say things that really hurt your feelings or made you feel like you were not wanted or loved?” Physical abuse was defined as being hit with a fist, kicked, or thrown down on the floor, into a wall, or down stairs. Sexual abuse included forced sexual touching or sexual relations.
Controlling for depression and anxiety weakened the associations between childhood abuse overall and likelihood of migraine in young adulthood, as well as for emotional abuse in particular, but the relationships remained statistically significant (OR, 1.32 and 1.33, respectively).
Dr. Tietjen said she was surprised by the absence of an association between migraine and physical and sexual abuse after controlling for other types of abuse.
“Sexual and physical abuse may be less frequent, occur over a briefer duration, and if limited, lead in some cases to resilience,” Dr. Tietjen noted. “Emotional abuse is likely more insidious, being ingrained in the fabric of the family dynamic. It may occur over years without recognition or intervention,” she said. “This type of abuse may cause more cumulative stress, with subsequent dysregulation of the HPA axis, immune, autonomic, and metabolic systems,” she added.
The study does not show cause and effect, the researchers noted, and more research is needed. But the findings suggest that clinicians might consider childhood abuse when counseling adult migraine patients.
“In migraineurs, childhood abuse, particularly emotional abuse, is common and possibly causally related,” Dr. Tietjen said. “Knowledge of adverse childhood experiences allows physicians to identify migraineurs at higher risk for psychiatric disease, pain comorbidities, and conditions associated with inflammation. These patients would likely benefit from exposure to cognitive behavioral therapy strategies, in order to decrease neurophysiological responses to stress,” she noted.
“There are currently therapies which reverse stress-induced epigenetic changes, which might be particularly useful in the subset of migraineurs who have been abused,” said Dr. Tietjen. Her next steps for research involve studying the effect of early life stress on factors such as pain sensitivity, anxiety, and depression.
The University of Toledo and the Clair Martig Endowment funded the study.
Emotionally abused children are 52% more likely to develop migraine in young adulthood than are those who were never abused, based on longitudinal survey data from nearly 15,000 individuals.
“Childhood maltreatment, and especially emotional abuse, is a common, likely under-recognized occurrence, which has enduring consequences for health throughout life. The association of emotional abuse with migraine has not heretofore been well studied, being the subject of only population-based study,” lead author Dr. Gretchen E. Tietjen of the University of Toledo (Ohio) said in an interview in advance of the presentation of the study at the annual meeting of the American Academy of Neurology in Vancouver in April.
Dr. Tietjen and her colleagues assessed data from 14,484 adults aged 24-32 years who took part in wave four of the National Longitudinal Study of Adolescent to Adult Health. Of these, 2,061 (14%) reported a migraine diagnosis, and 1,246 (60%) of those diagnosed with migraines reported some type of childhood abuse. A total of 6,088 (49%) individuals without migraine reported some type of childhood abuse.
Overall, the odds of migraine in adulthood was 55% higher in children who reported emotional abuse, physical abuse, or sexual abuse, compared with those who reported no childhood abuse, after controlling for age, race, sex, and income (odds ratio, 1.55; 95% confidence interval, 1.35-1.77). However, only emotional abuse remained significantly associated with increased odds for migraine after controlling for other types of abuse (OR, 1.52; 95% CI, 1.34-1.73).
Emotional abuse was assessed by asking, “How often did a parent or other adult caregiver say things that really hurt your feelings or made you feel like you were not wanted or loved?” Physical abuse was defined as being hit with a fist, kicked, or thrown down on the floor, into a wall, or down stairs. Sexual abuse included forced sexual touching or sexual relations.
Controlling for depression and anxiety weakened the associations between childhood abuse overall and likelihood of migraine in young adulthood, as well as for emotional abuse in particular, but the relationships remained statistically significant (OR, 1.32 and 1.33, respectively).
Dr. Tietjen said she was surprised by the absence of an association between migraine and physical and sexual abuse after controlling for other types of abuse.
“Sexual and physical abuse may be less frequent, occur over a briefer duration, and if limited, lead in some cases to resilience,” Dr. Tietjen noted. “Emotional abuse is likely more insidious, being ingrained in the fabric of the family dynamic. It may occur over years without recognition or intervention,” she said. “This type of abuse may cause more cumulative stress, with subsequent dysregulation of the HPA axis, immune, autonomic, and metabolic systems,” she added.
The study does not show cause and effect, the researchers noted, and more research is needed. But the findings suggest that clinicians might consider childhood abuse when counseling adult migraine patients.
“In migraineurs, childhood abuse, particularly emotional abuse, is common and possibly causally related,” Dr. Tietjen said. “Knowledge of adverse childhood experiences allows physicians to identify migraineurs at higher risk for psychiatric disease, pain comorbidities, and conditions associated with inflammation. These patients would likely benefit from exposure to cognitive behavioral therapy strategies, in order to decrease neurophysiological responses to stress,” she noted.
“There are currently therapies which reverse stress-induced epigenetic changes, which might be particularly useful in the subset of migraineurs who have been abused,” said Dr. Tietjen. Her next steps for research involve studying the effect of early life stress on factors such as pain sensitivity, anxiety, and depression.
The University of Toledo and the Clair Martig Endowment funded the study.
Emotionally abused children are 52% more likely to develop migraine in young adulthood than are those who were never abused, based on longitudinal survey data from nearly 15,000 individuals.
“Childhood maltreatment, and especially emotional abuse, is a common, likely under-recognized occurrence, which has enduring consequences for health throughout life. The association of emotional abuse with migraine has not heretofore been well studied, being the subject of only population-based study,” lead author Dr. Gretchen E. Tietjen of the University of Toledo (Ohio) said in an interview in advance of the presentation of the study at the annual meeting of the American Academy of Neurology in Vancouver in April.
Dr. Tietjen and her colleagues assessed data from 14,484 adults aged 24-32 years who took part in wave four of the National Longitudinal Study of Adolescent to Adult Health. Of these, 2,061 (14%) reported a migraine diagnosis, and 1,246 (60%) of those diagnosed with migraines reported some type of childhood abuse. A total of 6,088 (49%) individuals without migraine reported some type of childhood abuse.
Overall, the odds of migraine in adulthood was 55% higher in children who reported emotional abuse, physical abuse, or sexual abuse, compared with those who reported no childhood abuse, after controlling for age, race, sex, and income (odds ratio, 1.55; 95% confidence interval, 1.35-1.77). However, only emotional abuse remained significantly associated with increased odds for migraine after controlling for other types of abuse (OR, 1.52; 95% CI, 1.34-1.73).
Emotional abuse was assessed by asking, “How often did a parent or other adult caregiver say things that really hurt your feelings or made you feel like you were not wanted or loved?” Physical abuse was defined as being hit with a fist, kicked, or thrown down on the floor, into a wall, or down stairs. Sexual abuse included forced sexual touching or sexual relations.
Controlling for depression and anxiety weakened the associations between childhood abuse overall and likelihood of migraine in young adulthood, as well as for emotional abuse in particular, but the relationships remained statistically significant (OR, 1.32 and 1.33, respectively).
Dr. Tietjen said she was surprised by the absence of an association between migraine and physical and sexual abuse after controlling for other types of abuse.
“Sexual and physical abuse may be less frequent, occur over a briefer duration, and if limited, lead in some cases to resilience,” Dr. Tietjen noted. “Emotional abuse is likely more insidious, being ingrained in the fabric of the family dynamic. It may occur over years without recognition or intervention,” she said. “This type of abuse may cause more cumulative stress, with subsequent dysregulation of the HPA axis, immune, autonomic, and metabolic systems,” she added.
The study does not show cause and effect, the researchers noted, and more research is needed. But the findings suggest that clinicians might consider childhood abuse when counseling adult migraine patients.
“In migraineurs, childhood abuse, particularly emotional abuse, is common and possibly causally related,” Dr. Tietjen said. “Knowledge of adverse childhood experiences allows physicians to identify migraineurs at higher risk for psychiatric disease, pain comorbidities, and conditions associated with inflammation. These patients would likely benefit from exposure to cognitive behavioral therapy strategies, in order to decrease neurophysiological responses to stress,” she noted.
“There are currently therapies which reverse stress-induced epigenetic changes, which might be particularly useful in the subset of migraineurs who have been abused,” said Dr. Tietjen. Her next steps for research involve studying the effect of early life stress on factors such as pain sensitivity, anxiety, and depression.
The University of Toledo and the Clair Martig Endowment funded the study.
FROM THE AAN 2016 ANNUAL MEETING
Key clinical point: Childhood abuse had a significant effect on the likelihood of developing migraine in young adulthood, and emotional abuse was a stronger factor than physical or sexual abuse.
Major finding: Childhood abuse increased the odds of a migraine diagnosis in young adulthood by 55%; emotional abuse was associated with a 52% increased likelihood of migraine.
Data source: The data were taken from 14,484 adults aged 24-32 years in wave four of the National Longitudinal Study of Adolescent to Adult Health.
Disclosures: The University of Toledo and the Clair Martig Endowment funded the study.
Risperidone, aripiprazole treat irritability in children with ASD
Risperidone and aripiprazole, followed by N-acetylcysteine, appear most effective in treating irritability and aggression in youth with autism spectrum disorders (ASD), according to a systematic review and meta-analysis published in the February issue of Pediatrics.
“Although risperidone and aripiprazole have the strongest evidence for reducing ABC-I [Aberrant Behavioral Checklist–Irritability] in youth with autism spectrum disorders, they also have evidence for significant adverse events for a subset of patients,” reported Dr. Lawrence K. Fung of Stanford (Calif) University, and his associates (Pediatrics. 2016 Feb.;137[Suppl 2]:S124-35).
More than half of autistic individuals show significant emotion dysregulation, and about 20% have irritability or aggression at moderate to severe levels.
The authors combed Medline, PsychINFO, Embase, and review articles to identify randomized placebo-controlled trials evaluating medications to treat irritability and aggression in ASD youth, aged 2-17 years. The researchers used Aberrant Behavioral Checklist–Irritability scores as the primary endpoint in assessing effect size for improvement of emotional and behavioral symptoms in individuals with ASD.
Of 35 randomized controlled trials involving 1,673 participants included in the systematic review, 25 trials used the ABC-I, with 11 targeting irritability as the primary outcome and the other 14 targeting a different primary outcome. Five of the 11 trials targeting irritability tested the effectiveness of risperidone, while 2 tested aripiprazole, 2 tested valproate, 1 tested N-acetylcysteine, and 1 tested amantadine. Risperidone, aripiprazole, and N-acetylcysteine showed improvement in ABC-I scores with a moderate to large effect size. Valproate showed significant improvement to a lesser extent, but amantadine did not.
Among medications tested in the other 14 trials using the ABC-I, clonidine, methylphenidate, and tianeptine showed improvement with moderate effect sizes ,while venlafaxine and naltrexone showed improvement with a small effect size. Other medications tested included atomoxetine, citalopram, dextromethorphan, levetiracetam, mecamylamine, omega-3 fatty acid, and secretin. Hyperactivity and impulsivity improved in trials testing atomoxetine and dextromethorphan.
In trials using assessments other than ABC-I, risperidone and haloperidol showed effectiveness, compared with placebos, although risperidone beat haloperidol in a head-to-head trial. Some improvement in irritability also occurred with clomipramine, naltrexone, and a supplement with 19 vitamins and 9 minerals, compared with placebo.
The researchers calculated a number needed to treat (NNT) of two for risperidone at a dose between 1.2 and 1.9 mg, but the number needed to harm (NNH) for sedation from risperidone was also two. Risperidone’s NNH for extrapyramidal symptoms was six to seven. Flexible dosing with aripiprazole yielded an NNT of three, but fixed dosing led to an NNT of five to seven. The NNH for sedation with aripiprazole was 16, and the NNH for extrapyramidal symptoms was 20.
Sedation also occurred with haloperidol (NNH = 1) and amantadine (NNH = 10), and haloperidol caused extrapyramidal symptoms (NNH = 10). Weight gain occurred with risperidone, aripiprazole, and valproate.
“The reason for more compounds failing to show efficacy is not clear, but some of the negative studies had small sample sizes,” the authors noted. “Therefore, it is possible that some of these negative studies may represent false negatives,” and some of the studies used baseline ABC-I scores below the typical cutoff of at least 18 for inclusion.
The research was conducted through the Autism Speaks Autism Treatment Network and was supported by the U.S. Department of Health and Human Services, and the maternal and child health research program at Massachusetts General Hospital. Dr. Daniel Coury has received research funding from Autism Speaks, SynapDx, and Neuren Pharmaceuticals; has consulted for Cognoa; and is a speaker for Abbott/Innovative Biopharma. Dr. Jeremy Veenstra-VanderWeele has received research funding from Seaside Therapeutics, Roche Pharmaceuticals, Novartis, Forest, Sunovion, and SynapDx and has consulted for or advised Roche Pharmaceuticals, SynapDx, and Novartis.
Risperidone and aripiprazole, followed by N-acetylcysteine, appear most effective in treating irritability and aggression in youth with autism spectrum disorders (ASD), according to a systematic review and meta-analysis published in the February issue of Pediatrics.
“Although risperidone and aripiprazole have the strongest evidence for reducing ABC-I [Aberrant Behavioral Checklist–Irritability] in youth with autism spectrum disorders, they also have evidence for significant adverse events for a subset of patients,” reported Dr. Lawrence K. Fung of Stanford (Calif) University, and his associates (Pediatrics. 2016 Feb.;137[Suppl 2]:S124-35).
More than half of autistic individuals show significant emotion dysregulation, and about 20% have irritability or aggression at moderate to severe levels.
The authors combed Medline, PsychINFO, Embase, and review articles to identify randomized placebo-controlled trials evaluating medications to treat irritability and aggression in ASD youth, aged 2-17 years. The researchers used Aberrant Behavioral Checklist–Irritability scores as the primary endpoint in assessing effect size for improvement of emotional and behavioral symptoms in individuals with ASD.
Of 35 randomized controlled trials involving 1,673 participants included in the systematic review, 25 trials used the ABC-I, with 11 targeting irritability as the primary outcome and the other 14 targeting a different primary outcome. Five of the 11 trials targeting irritability tested the effectiveness of risperidone, while 2 tested aripiprazole, 2 tested valproate, 1 tested N-acetylcysteine, and 1 tested amantadine. Risperidone, aripiprazole, and N-acetylcysteine showed improvement in ABC-I scores with a moderate to large effect size. Valproate showed significant improvement to a lesser extent, but amantadine did not.
Among medications tested in the other 14 trials using the ABC-I, clonidine, methylphenidate, and tianeptine showed improvement with moderate effect sizes ,while venlafaxine and naltrexone showed improvement with a small effect size. Other medications tested included atomoxetine, citalopram, dextromethorphan, levetiracetam, mecamylamine, omega-3 fatty acid, and secretin. Hyperactivity and impulsivity improved in trials testing atomoxetine and dextromethorphan.
In trials using assessments other than ABC-I, risperidone and haloperidol showed effectiveness, compared with placebos, although risperidone beat haloperidol in a head-to-head trial. Some improvement in irritability also occurred with clomipramine, naltrexone, and a supplement with 19 vitamins and 9 minerals, compared with placebo.
The researchers calculated a number needed to treat (NNT) of two for risperidone at a dose between 1.2 and 1.9 mg, but the number needed to harm (NNH) for sedation from risperidone was also two. Risperidone’s NNH for extrapyramidal symptoms was six to seven. Flexible dosing with aripiprazole yielded an NNT of three, but fixed dosing led to an NNT of five to seven. The NNH for sedation with aripiprazole was 16, and the NNH for extrapyramidal symptoms was 20.
Sedation also occurred with haloperidol (NNH = 1) and amantadine (NNH = 10), and haloperidol caused extrapyramidal symptoms (NNH = 10). Weight gain occurred with risperidone, aripiprazole, and valproate.
“The reason for more compounds failing to show efficacy is not clear, but some of the negative studies had small sample sizes,” the authors noted. “Therefore, it is possible that some of these negative studies may represent false negatives,” and some of the studies used baseline ABC-I scores below the typical cutoff of at least 18 for inclusion.
The research was conducted through the Autism Speaks Autism Treatment Network and was supported by the U.S. Department of Health and Human Services, and the maternal and child health research program at Massachusetts General Hospital. Dr. Daniel Coury has received research funding from Autism Speaks, SynapDx, and Neuren Pharmaceuticals; has consulted for Cognoa; and is a speaker for Abbott/Innovative Biopharma. Dr. Jeremy Veenstra-VanderWeele has received research funding from Seaside Therapeutics, Roche Pharmaceuticals, Novartis, Forest, Sunovion, and SynapDx and has consulted for or advised Roche Pharmaceuticals, SynapDx, and Novartis.
Risperidone and aripiprazole, followed by N-acetylcysteine, appear most effective in treating irritability and aggression in youth with autism spectrum disorders (ASD), according to a systematic review and meta-analysis published in the February issue of Pediatrics.
“Although risperidone and aripiprazole have the strongest evidence for reducing ABC-I [Aberrant Behavioral Checklist–Irritability] in youth with autism spectrum disorders, they also have evidence for significant adverse events for a subset of patients,” reported Dr. Lawrence K. Fung of Stanford (Calif) University, and his associates (Pediatrics. 2016 Feb.;137[Suppl 2]:S124-35).
More than half of autistic individuals show significant emotion dysregulation, and about 20% have irritability or aggression at moderate to severe levels.
The authors combed Medline, PsychINFO, Embase, and review articles to identify randomized placebo-controlled trials evaluating medications to treat irritability and aggression in ASD youth, aged 2-17 years. The researchers used Aberrant Behavioral Checklist–Irritability scores as the primary endpoint in assessing effect size for improvement of emotional and behavioral symptoms in individuals with ASD.
Of 35 randomized controlled trials involving 1,673 participants included in the systematic review, 25 trials used the ABC-I, with 11 targeting irritability as the primary outcome and the other 14 targeting a different primary outcome. Five of the 11 trials targeting irritability tested the effectiveness of risperidone, while 2 tested aripiprazole, 2 tested valproate, 1 tested N-acetylcysteine, and 1 tested amantadine. Risperidone, aripiprazole, and N-acetylcysteine showed improvement in ABC-I scores with a moderate to large effect size. Valproate showed significant improvement to a lesser extent, but amantadine did not.
Among medications tested in the other 14 trials using the ABC-I, clonidine, methylphenidate, and tianeptine showed improvement with moderate effect sizes ,while venlafaxine and naltrexone showed improvement with a small effect size. Other medications tested included atomoxetine, citalopram, dextromethorphan, levetiracetam, mecamylamine, omega-3 fatty acid, and secretin. Hyperactivity and impulsivity improved in trials testing atomoxetine and dextromethorphan.
In trials using assessments other than ABC-I, risperidone and haloperidol showed effectiveness, compared with placebos, although risperidone beat haloperidol in a head-to-head trial. Some improvement in irritability also occurred with clomipramine, naltrexone, and a supplement with 19 vitamins and 9 minerals, compared with placebo.
The researchers calculated a number needed to treat (NNT) of two for risperidone at a dose between 1.2 and 1.9 mg, but the number needed to harm (NNH) for sedation from risperidone was also two. Risperidone’s NNH for extrapyramidal symptoms was six to seven. Flexible dosing with aripiprazole yielded an NNT of three, but fixed dosing led to an NNT of five to seven. The NNH for sedation with aripiprazole was 16, and the NNH for extrapyramidal symptoms was 20.
Sedation also occurred with haloperidol (NNH = 1) and amantadine (NNH = 10), and haloperidol caused extrapyramidal symptoms (NNH = 10). Weight gain occurred with risperidone, aripiprazole, and valproate.
“The reason for more compounds failing to show efficacy is not clear, but some of the negative studies had small sample sizes,” the authors noted. “Therefore, it is possible that some of these negative studies may represent false negatives,” and some of the studies used baseline ABC-I scores below the typical cutoff of at least 18 for inclusion.
The research was conducted through the Autism Speaks Autism Treatment Network and was supported by the U.S. Department of Health and Human Services, and the maternal and child health research program at Massachusetts General Hospital. Dr. Daniel Coury has received research funding from Autism Speaks, SynapDx, and Neuren Pharmaceuticals; has consulted for Cognoa; and is a speaker for Abbott/Innovative Biopharma. Dr. Jeremy Veenstra-VanderWeele has received research funding from Seaside Therapeutics, Roche Pharmaceuticals, Novartis, Forest, Sunovion, and SynapDx and has consulted for or advised Roche Pharmaceuticals, SynapDx, and Novartis.
FROM PEDIATRICS
Key clinical point: Risperidone and aripiprazole most effectively treat irritability and aggression in youth with autism spectrum disorders.
Major finding: The number needed to treat was two for risperidone and three with flexible dosing of aripiprazole, with varying numbers needed to harm depending on adverse events.
Data source: A systematic review and meta-analysis of 35 randomized controlled studies assessing the effectiveness of medications in the treatment of irritability and aggression in youth with ASD.
Disclosures: The research was conducted through the Autism Speaks Autism Treatment Network and was supported by the U.S. Department of Health and Human Services, and the maternal and child health research program at Massachusetts General Hospital. Dr. Daniel Coury has received research funding from Autism Speaks, SynapDx, and Neuren Pharmaceuticals; has consulted for Cognoa; and is a speaker for Abbott/Innovative Biopharma. Dr. Jeremy Veenstra-VanderWeele has received research funding from Seaside Therapeutics, Roche Pharmaceuticals, Novartis, Forest, Sunovion, and SynapDx and has consulted for or advised Roche Pharmaceuticals, SynapDx, and Novartis.
Earlier intervention urged in prodromal depression, anxiety
LAS VEGAS – If a published study ever challenged the way Dr. Joseph R. Calabrese thinks about mental and substance use disorders, it was the Global Burden of Disease Study 2010, which evaluated 291 illnesses in 187 countries worldwide from 1990-2010.
It found that mental and substance use disorders are the most disabling disorders worldwide, ranking No. 1 in years lost because of disability, No. 5 in disability-adjusted life years, and No. 9 in years of life lost (Lancet. 2013 Nov;382:1757-86). “The take-home message from this study is, don’t wait until illness becomes syndromal,” Dr. Calabrese said at the annual psychopharmacology update held by the Nevada Psychiatric Association. “Early intervention is not only appropriate in all of medicine, but it’s appropriate for us.”
Dr. Calabrese, director of the Mood Disorders Program at Case Western Reserve University, Cleveland, said the findings support other work that reconceptualizes mental and substance use disorders as neurodevelopmental disorders. Pathophysiological changes begin during fetal and/or early postnatal life, followed by delayed onset of symptoms. In fact, “50% of people have the onset of illness by age 15, and 75% by age 25,” he said. “This is really important, because as a field, I don’t think we’ve been that aggressive in treating prodromal presentations or subsyndromal presentations.”
A key finding from the Global Burden of Disease Study 2010, which he characterized as “groundbreaking,” is that the burden associated with depression and anxiety rises abruptly in childhood (ages 1-10), and then peaks during adolescence and young adulthood (ages 10-29). “This is a big deal,” said Dr. Calabrese, who is also the Bipolar Disorders Research Chair and professor of psychiatry at the university. “Maybe from the perspective of our discipline, this isn’t something that’s actionable, but mothers know this. They usually say, ‘I could have told you so.’ We have to be more aggressive, and we have to intervene earlier, especially in the presence of family history.”
Prior to the Global Burden of Disease Study 2010, he continued, researchers had never evaluated the trajectories of morbidity and mortality of mental and substance use disorders. The study found that depression emerges first, and quickly worsens during childhood and adolescence. “It’s incumbent upon us to diagnose and treat depression in childhood, because it worsens quickly, and it peaks robustly around the mid-20s,” he said. Anxiety confers “about half as much morbidity” as depression, “but it still peaks in childhood, and the severity is less than half that of depression,” he said. “Clinically, this rings true to me. Parents will typically say that their child has been anxious since birth.”
According to the Global Burden of Disease Study 2010, bipolar disorder and schizophrenia emerge during adolescence and young adulthood, and reach peak severity during ages 30-40. Worldwide morbidity from bipolar disorder and schizophrenia is not as severe as that from depression. The study also found that mood and anxiety disorders precede drug and alcohol dependence by about 10 years. “To me, as a clinician, this is extremely important,” Dr. Calabrese said. “We should not only recognize and treat depression and anxiety, because they’re bad illnesses, but if we don’t intervene early, [they] lead to drug dependence and alcohol dependence. Drug dependence is worse than alcohol dependence, and it peaks earlier.”
Dr. Calabrese went on to note that major depressive disorder (MDD) continues to be the most common misdiagnosis in bipolar disorder, an issue that “has huge ramifications.” One study found that about half of properly diagnosed hospitalized patients with MDD convert to bipolar depression over 20 years, at a constant rate of 0.5% and 1% per year for bipolar I and bipolar II, respectively (J Affect Disord. 2005 Feb; 84[2-3]:149-57). “The big question that has intrigued a lot of people is, how do you distinguish bipolar disorder from MDD?” he asked. “There is no one place where MDD stops and bipolar disorder begins. Most patients have most symptoms of both illnesses. In our nomenclature, we’re supposed to say, ‘mania with mixed features,’ or ‘depression with mixed features,’ but it doesn’t work that way. From a clinical perspective, it means anything goes when it comes to treating people in the middle. The thing to do is look for symptoms of the other phase of the illness. The more symptoms you see at the other phase of the illness, treat that patient as if they had the other illness.”
Patients with bipolar disorder live the majority of their symptomatic lives in the depressed phase of the illness, he continued. In fact, one study estimated that the ratio of time spent depressed to hypomanic symptoms is 39:1 in bipolar II and 3:1 in bipolar I (Arch Gen Psychiatry. 2003 Mar; 60[3]:261-9). Patients with bipolar I disorder “are not that hard to diagnose, but digging out hypomania in somebody who has spent a large portion of their time depressed is really difficult to do,” Dr. Calabrese said. “It’s just not possible, unless we meet with the family at the same time. Patients either don’t remember the symptoms they had when they were manic or mixed, or they don’t want to talk about it.”
He concluded his remarks by revisiting the Global Burden of Disease study, which found that patients with mental and substance use face a lifespan that’s shortened by an average of 10 years. Some 67% of this premature mortality is tied to the earlier onset of chronic conditions such as cardiovascular disease, diabetes mellitus, and chronic obstructive pulmonary disease, while suicide only accounted for 17.5% of early deaths. “Therefore, when treating bipolar disorder, look for co-occurring medical illness, signs of metabolic burden, and unhealthy lifestyle behaviors, such as obesity, smoking, physical inactivity, and poor diet,” he said. Other emerging data suggest that in patients with bipolar disorder, premature death tied to cardiovascular disease exceeds that tied to suicide (Ann Clin Psychiatry. 2011 Feb;23[1]:40-7). “It’s almost as if we need a nurse seeing our patients before or after we see them, to counsel them about healthy living and how, over time, lifespan is shortened if you don’t get this illness treated,” he said.
Dr. Calabrese reported having numerous financial ties to the pharmaceutical industry.
LAS VEGAS – If a published study ever challenged the way Dr. Joseph R. Calabrese thinks about mental and substance use disorders, it was the Global Burden of Disease Study 2010, which evaluated 291 illnesses in 187 countries worldwide from 1990-2010.
It found that mental and substance use disorders are the most disabling disorders worldwide, ranking No. 1 in years lost because of disability, No. 5 in disability-adjusted life years, and No. 9 in years of life lost (Lancet. 2013 Nov;382:1757-86). “The take-home message from this study is, don’t wait until illness becomes syndromal,” Dr. Calabrese said at the annual psychopharmacology update held by the Nevada Psychiatric Association. “Early intervention is not only appropriate in all of medicine, but it’s appropriate for us.”
Dr. Calabrese, director of the Mood Disorders Program at Case Western Reserve University, Cleveland, said the findings support other work that reconceptualizes mental and substance use disorders as neurodevelopmental disorders. Pathophysiological changes begin during fetal and/or early postnatal life, followed by delayed onset of symptoms. In fact, “50% of people have the onset of illness by age 15, and 75% by age 25,” he said. “This is really important, because as a field, I don’t think we’ve been that aggressive in treating prodromal presentations or subsyndromal presentations.”
A key finding from the Global Burden of Disease Study 2010, which he characterized as “groundbreaking,” is that the burden associated with depression and anxiety rises abruptly in childhood (ages 1-10), and then peaks during adolescence and young adulthood (ages 10-29). “This is a big deal,” said Dr. Calabrese, who is also the Bipolar Disorders Research Chair and professor of psychiatry at the university. “Maybe from the perspective of our discipline, this isn’t something that’s actionable, but mothers know this. They usually say, ‘I could have told you so.’ We have to be more aggressive, and we have to intervene earlier, especially in the presence of family history.”
Prior to the Global Burden of Disease Study 2010, he continued, researchers had never evaluated the trajectories of morbidity and mortality of mental and substance use disorders. The study found that depression emerges first, and quickly worsens during childhood and adolescence. “It’s incumbent upon us to diagnose and treat depression in childhood, because it worsens quickly, and it peaks robustly around the mid-20s,” he said. Anxiety confers “about half as much morbidity” as depression, “but it still peaks in childhood, and the severity is less than half that of depression,” he said. “Clinically, this rings true to me. Parents will typically say that their child has been anxious since birth.”
According to the Global Burden of Disease Study 2010, bipolar disorder and schizophrenia emerge during adolescence and young adulthood, and reach peak severity during ages 30-40. Worldwide morbidity from bipolar disorder and schizophrenia is not as severe as that from depression. The study also found that mood and anxiety disorders precede drug and alcohol dependence by about 10 years. “To me, as a clinician, this is extremely important,” Dr. Calabrese said. “We should not only recognize and treat depression and anxiety, because they’re bad illnesses, but if we don’t intervene early, [they] lead to drug dependence and alcohol dependence. Drug dependence is worse than alcohol dependence, and it peaks earlier.”
Dr. Calabrese went on to note that major depressive disorder (MDD) continues to be the most common misdiagnosis in bipolar disorder, an issue that “has huge ramifications.” One study found that about half of properly diagnosed hospitalized patients with MDD convert to bipolar depression over 20 years, at a constant rate of 0.5% and 1% per year for bipolar I and bipolar II, respectively (J Affect Disord. 2005 Feb; 84[2-3]:149-57). “The big question that has intrigued a lot of people is, how do you distinguish bipolar disorder from MDD?” he asked. “There is no one place where MDD stops and bipolar disorder begins. Most patients have most symptoms of both illnesses. In our nomenclature, we’re supposed to say, ‘mania with mixed features,’ or ‘depression with mixed features,’ but it doesn’t work that way. From a clinical perspective, it means anything goes when it comes to treating people in the middle. The thing to do is look for symptoms of the other phase of the illness. The more symptoms you see at the other phase of the illness, treat that patient as if they had the other illness.”
Patients with bipolar disorder live the majority of their symptomatic lives in the depressed phase of the illness, he continued. In fact, one study estimated that the ratio of time spent depressed to hypomanic symptoms is 39:1 in bipolar II and 3:1 in bipolar I (Arch Gen Psychiatry. 2003 Mar; 60[3]:261-9). Patients with bipolar I disorder “are not that hard to diagnose, but digging out hypomania in somebody who has spent a large portion of their time depressed is really difficult to do,” Dr. Calabrese said. “It’s just not possible, unless we meet with the family at the same time. Patients either don’t remember the symptoms they had when they were manic or mixed, or they don’t want to talk about it.”
He concluded his remarks by revisiting the Global Burden of Disease study, which found that patients with mental and substance use face a lifespan that’s shortened by an average of 10 years. Some 67% of this premature mortality is tied to the earlier onset of chronic conditions such as cardiovascular disease, diabetes mellitus, and chronic obstructive pulmonary disease, while suicide only accounted for 17.5% of early deaths. “Therefore, when treating bipolar disorder, look for co-occurring medical illness, signs of metabolic burden, and unhealthy lifestyle behaviors, such as obesity, smoking, physical inactivity, and poor diet,” he said. Other emerging data suggest that in patients with bipolar disorder, premature death tied to cardiovascular disease exceeds that tied to suicide (Ann Clin Psychiatry. 2011 Feb;23[1]:40-7). “It’s almost as if we need a nurse seeing our patients before or after we see them, to counsel them about healthy living and how, over time, lifespan is shortened if you don’t get this illness treated,” he said.
Dr. Calabrese reported having numerous financial ties to the pharmaceutical industry.
LAS VEGAS – If a published study ever challenged the way Dr. Joseph R. Calabrese thinks about mental and substance use disorders, it was the Global Burden of Disease Study 2010, which evaluated 291 illnesses in 187 countries worldwide from 1990-2010.
It found that mental and substance use disorders are the most disabling disorders worldwide, ranking No. 1 in years lost because of disability, No. 5 in disability-adjusted life years, and No. 9 in years of life lost (Lancet. 2013 Nov;382:1757-86). “The take-home message from this study is, don’t wait until illness becomes syndromal,” Dr. Calabrese said at the annual psychopharmacology update held by the Nevada Psychiatric Association. “Early intervention is not only appropriate in all of medicine, but it’s appropriate for us.”
Dr. Calabrese, director of the Mood Disorders Program at Case Western Reserve University, Cleveland, said the findings support other work that reconceptualizes mental and substance use disorders as neurodevelopmental disorders. Pathophysiological changes begin during fetal and/or early postnatal life, followed by delayed onset of symptoms. In fact, “50% of people have the onset of illness by age 15, and 75% by age 25,” he said. “This is really important, because as a field, I don’t think we’ve been that aggressive in treating prodromal presentations or subsyndromal presentations.”
A key finding from the Global Burden of Disease Study 2010, which he characterized as “groundbreaking,” is that the burden associated with depression and anxiety rises abruptly in childhood (ages 1-10), and then peaks during adolescence and young adulthood (ages 10-29). “This is a big deal,” said Dr. Calabrese, who is also the Bipolar Disorders Research Chair and professor of psychiatry at the university. “Maybe from the perspective of our discipline, this isn’t something that’s actionable, but mothers know this. They usually say, ‘I could have told you so.’ We have to be more aggressive, and we have to intervene earlier, especially in the presence of family history.”
Prior to the Global Burden of Disease Study 2010, he continued, researchers had never evaluated the trajectories of morbidity and mortality of mental and substance use disorders. The study found that depression emerges first, and quickly worsens during childhood and adolescence. “It’s incumbent upon us to diagnose and treat depression in childhood, because it worsens quickly, and it peaks robustly around the mid-20s,” he said. Anxiety confers “about half as much morbidity” as depression, “but it still peaks in childhood, and the severity is less than half that of depression,” he said. “Clinically, this rings true to me. Parents will typically say that their child has been anxious since birth.”
According to the Global Burden of Disease Study 2010, bipolar disorder and schizophrenia emerge during adolescence and young adulthood, and reach peak severity during ages 30-40. Worldwide morbidity from bipolar disorder and schizophrenia is not as severe as that from depression. The study also found that mood and anxiety disorders precede drug and alcohol dependence by about 10 years. “To me, as a clinician, this is extremely important,” Dr. Calabrese said. “We should not only recognize and treat depression and anxiety, because they’re bad illnesses, but if we don’t intervene early, [they] lead to drug dependence and alcohol dependence. Drug dependence is worse than alcohol dependence, and it peaks earlier.”
Dr. Calabrese went on to note that major depressive disorder (MDD) continues to be the most common misdiagnosis in bipolar disorder, an issue that “has huge ramifications.” One study found that about half of properly diagnosed hospitalized patients with MDD convert to bipolar depression over 20 years, at a constant rate of 0.5% and 1% per year for bipolar I and bipolar II, respectively (J Affect Disord. 2005 Feb; 84[2-3]:149-57). “The big question that has intrigued a lot of people is, how do you distinguish bipolar disorder from MDD?” he asked. “There is no one place where MDD stops and bipolar disorder begins. Most patients have most symptoms of both illnesses. In our nomenclature, we’re supposed to say, ‘mania with mixed features,’ or ‘depression with mixed features,’ but it doesn’t work that way. From a clinical perspective, it means anything goes when it comes to treating people in the middle. The thing to do is look for symptoms of the other phase of the illness. The more symptoms you see at the other phase of the illness, treat that patient as if they had the other illness.”
Patients with bipolar disorder live the majority of their symptomatic lives in the depressed phase of the illness, he continued. In fact, one study estimated that the ratio of time spent depressed to hypomanic symptoms is 39:1 in bipolar II and 3:1 in bipolar I (Arch Gen Psychiatry. 2003 Mar; 60[3]:261-9). Patients with bipolar I disorder “are not that hard to diagnose, but digging out hypomania in somebody who has spent a large portion of their time depressed is really difficult to do,” Dr. Calabrese said. “It’s just not possible, unless we meet with the family at the same time. Patients either don’t remember the symptoms they had when they were manic or mixed, or they don’t want to talk about it.”
He concluded his remarks by revisiting the Global Burden of Disease study, which found that patients with mental and substance use face a lifespan that’s shortened by an average of 10 years. Some 67% of this premature mortality is tied to the earlier onset of chronic conditions such as cardiovascular disease, diabetes mellitus, and chronic obstructive pulmonary disease, while suicide only accounted for 17.5% of early deaths. “Therefore, when treating bipolar disorder, look for co-occurring medical illness, signs of metabolic burden, and unhealthy lifestyle behaviors, such as obesity, smoking, physical inactivity, and poor diet,” he said. Other emerging data suggest that in patients with bipolar disorder, premature death tied to cardiovascular disease exceeds that tied to suicide (Ann Clin Psychiatry. 2011 Feb;23[1]:40-7). “It’s almost as if we need a nurse seeing our patients before or after we see them, to counsel them about healthy living and how, over time, lifespan is shortened if you don’t get this illness treated,” he said.
Dr. Calabrese reported having numerous financial ties to the pharmaceutical industry.
