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New measles outbreak reported in western N.Y.
A new measles outbreak in western New York has affected five people within a Mennonite community, according to the New York State Department of Health.
The five cases in Wyoming County, located east of Buffalo, were reported Aug. 8 and no further cases have been confirmed as of Aug. 16, the county health department said on its website.
Those five cases, along with six new cases in Rockland County, N.Y., and 10 more around the country, brought the total for the Centers for Disease Control and Prevention’s latest reporting week to 21 and the total for the year to 1,203, the CDC said Aug. 19.
Along with Wyoming County and Rockland County (296 cases since Sept. 2018), the CDC currently is tracking outbreaks in New York City (653 cases since Sept. 2018), Washington state (85 cases in 2019; 13 in the current outbreak), California (65 cases in 2019; 5 in the current outbreak), and Texas (21 cases in 2019; 6 in the current outbreak).
“More than 75% of the cases this year are linked to outbreaks in New York and New York City,” the CDC said on its website, while also noting that “124 of the people who got measles this year were hospitalized, and 64 reported having complications, including pneumonia and encephalitis.”
A new measles outbreak in western New York has affected five people within a Mennonite community, according to the New York State Department of Health.
The five cases in Wyoming County, located east of Buffalo, were reported Aug. 8 and no further cases have been confirmed as of Aug. 16, the county health department said on its website.
Those five cases, along with six new cases in Rockland County, N.Y., and 10 more around the country, brought the total for the Centers for Disease Control and Prevention’s latest reporting week to 21 and the total for the year to 1,203, the CDC said Aug. 19.
Along with Wyoming County and Rockland County (296 cases since Sept. 2018), the CDC currently is tracking outbreaks in New York City (653 cases since Sept. 2018), Washington state (85 cases in 2019; 13 in the current outbreak), California (65 cases in 2019; 5 in the current outbreak), and Texas (21 cases in 2019; 6 in the current outbreak).
“More than 75% of the cases this year are linked to outbreaks in New York and New York City,” the CDC said on its website, while also noting that “124 of the people who got measles this year were hospitalized, and 64 reported having complications, including pneumonia and encephalitis.”
A new measles outbreak in western New York has affected five people within a Mennonite community, according to the New York State Department of Health.
The five cases in Wyoming County, located east of Buffalo, were reported Aug. 8 and no further cases have been confirmed as of Aug. 16, the county health department said on its website.
Those five cases, along with six new cases in Rockland County, N.Y., and 10 more around the country, brought the total for the Centers for Disease Control and Prevention’s latest reporting week to 21 and the total for the year to 1,203, the CDC said Aug. 19.
Along with Wyoming County and Rockland County (296 cases since Sept. 2018), the CDC currently is tracking outbreaks in New York City (653 cases since Sept. 2018), Washington state (85 cases in 2019; 13 in the current outbreak), California (65 cases in 2019; 5 in the current outbreak), and Texas (21 cases in 2019; 6 in the current outbreak).
“More than 75% of the cases this year are linked to outbreaks in New York and New York City,” the CDC said on its website, while also noting that “124 of the people who got measles this year were hospitalized, and 64 reported having complications, including pneumonia and encephalitis.”
Fluoride exposure during pregnancy tied to lower IQ score in children
with boys having a lower mean score than girls, according to a recent prospective, multicenter birth cohort study.
“These findings were observed at fluoride levels typically found in white North American women,” wrote Rivka Green, York University, Toronto, and colleagues. “This indicates the possible need to reduce fluoride intake during pregnancy.”
This study confirms findings in a 2017 study suggesting a relationship between maternal fluoride levels and children’s later cognitive scores.
Ms. Green and colleagues evaluated 512 mother-child pairs in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort from six Canadian cities. The children were born between 2008 and 2012, underwent neurodevelopmental testing between 3 and 4 years, and were assessed using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. Full Scale IQ (FSIQ) test.
Of these, 400 mother-child pairs had data on fluoride intake, IQ, and complete covariate data; 141 of these mothers lived in areas with fluoridated tap water, while 228 mothers lived in areas without fluoridated tap water. Maternal urinary fluoride adjusted for specific gravity (MUFSG) was averaged across three trimesters of data, and the estimated fluoride level was obtained through self-reported exposure by women included in the study.
The researchers found mothers living in areas with fluoridated water had significantly higher MUFSG levels (0.69 mg/L), compared with women in areas without fluoridated water (0.40 mg/L; P equals .001). The median estimated fluoride intake was significantly higher among women living in areas with fluoridated water (0.93 mg per day) than in women who did not live in areas with fluoridated water (0.30 mg per day; P less than .001).
Overall, children scored a mean 107.16 (range, 52-143) on the IQ test, and girls had significantly higher mean IQ scores than did boys (109.56 vs. 104.61; P = .001). After adjusting for covariates of maternal age, race, parity, smoking, and alcohol status during pregnancy, child gender, gestational age, and birth weight, the researchers found a significant interaction between MUFSG and the child’s gender (P = .02), and a 1-mg/L MUFSG increase was associated with a decrease in 4.49 IQ points in boys (95% confidence interval, −8.38 to −0.60) but not girls. There also was an association between 1-mg higher daily intake of maternal fluoride intake and decreased IQ score in both boys and girls (−3.66; 95% CI, −7.16 to −0.15 ; P = .04).
Ms. Green and her colleagues acknowledged several limitations with the study, such as the short half-life of urinary fluoride and the potential inaccuracy of maternal urinary samples at predicting fetal exposure to fluoride, the self-reported nature of estimated fluoride consumption, lack of availability of maternal IQ data, and not including postnatal exposure and consumption of fluoride.
In a related editorial, David C. Bellinger, PhD, MSc, referred to a previous prospective study in Mexico City by Bashash et al. that found a maternal fluoride level of 0.9 mg/L was associated with a decrease in cognitive scores in children at 4 years and between 6 years and 12 years (Environ Health Perspect. 2017;125(9):097017. doi: 10.1289/EHP655), and noted the effect sizes seen in the Mexico City study were similar to those reported by Green et al. “If the effect sizes reported by Green et al. and others are valid, the total cognitive loss at the population level that might be associated with children’s prenatal exposure to fluoride could be substantial,” he said.
The study raises many questions, including whether there is a concentration where neurotoxicity risk is negligible, if gender plays a role (there was no gender risk difference in Bashash et al.), whether other developmental domains are affected apart from IQ, and if postnatal exposure carries a risk, Dr. Bellinger said. “The findings of Green et al. and others indicate that a dispassionate and tempered discussion of fluoride’s potential neurotoxicity is warranted, including consideration of what additional research is needed to reach more definitive conclusions about the implications, if any, for public health,” he said.
Dimitri A. Christakis, MD, MPH, editor of JAMA Pediatrics and director of the Center for Child Health, Behavior, and Development at Seattle Children’s Research Institute, said in an editor’s note that it was not an easy decision to publish the article because of the potential implications of the findings.
“The mission of the journal is to ensure that child health is optimized by bringing the best available evidence to the fore,” he said. “Publishing it serves as testament to the fact that JAMA Pediatrics is committed to disseminating the best science based entirely on the rigor of the methods and the soundness of the hypotheses tested, regardless of how contentious the results may be.”
However, “scientific inquiry is an iterative process,” Dr. Christakis said, and rarely does a single study provide “definitive evidence.
“We hope that purveyors and consumers of these findings are mindful of that as the implications of this study are debated in the public arena.”
This study was funded in a grant from the National Institute of Environmental Health Science, and the MIREC Study was funded by Chemicals Management Plan at Health Canada, the Ontario Ministry of the Environment, and the Canadian Institutes for Health Research. Dr. Bruce Lanphear reported being an unpaid expert witness for an upcoming case involving the U.S. Environmental Protection Agency and water fluoridation. Dr. Richard Hornung reported receiving personal fees from York University. Dr. E. Angeles Martinez-Mier reported receiving grants from the National Institutes of Health. The other authors report no relevant conflicts of interest. Dr. Bellinger reported no relevant conflicts of interest with regard to his editorial.
SOURCEs: Green R et al. JAMA Pediatr. 2019. doi: 10.1001/jamapediatrics.2019.1729; Bellinger. JAMA Pediatr. 2019. doi: 10.1001/ jamapediatrics.2019.1728.
with boys having a lower mean score than girls, according to a recent prospective, multicenter birth cohort study.
“These findings were observed at fluoride levels typically found in white North American women,” wrote Rivka Green, York University, Toronto, and colleagues. “This indicates the possible need to reduce fluoride intake during pregnancy.”
This study confirms findings in a 2017 study suggesting a relationship between maternal fluoride levels and children’s later cognitive scores.
Ms. Green and colleagues evaluated 512 mother-child pairs in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort from six Canadian cities. The children were born between 2008 and 2012, underwent neurodevelopmental testing between 3 and 4 years, and were assessed using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. Full Scale IQ (FSIQ) test.
Of these, 400 mother-child pairs had data on fluoride intake, IQ, and complete covariate data; 141 of these mothers lived in areas with fluoridated tap water, while 228 mothers lived in areas without fluoridated tap water. Maternal urinary fluoride adjusted for specific gravity (MUFSG) was averaged across three trimesters of data, and the estimated fluoride level was obtained through self-reported exposure by women included in the study.
The researchers found mothers living in areas with fluoridated water had significantly higher MUFSG levels (0.69 mg/L), compared with women in areas without fluoridated water (0.40 mg/L; P equals .001). The median estimated fluoride intake was significantly higher among women living in areas with fluoridated water (0.93 mg per day) than in women who did not live in areas with fluoridated water (0.30 mg per day; P less than .001).
Overall, children scored a mean 107.16 (range, 52-143) on the IQ test, and girls had significantly higher mean IQ scores than did boys (109.56 vs. 104.61; P = .001). After adjusting for covariates of maternal age, race, parity, smoking, and alcohol status during pregnancy, child gender, gestational age, and birth weight, the researchers found a significant interaction between MUFSG and the child’s gender (P = .02), and a 1-mg/L MUFSG increase was associated with a decrease in 4.49 IQ points in boys (95% confidence interval, −8.38 to −0.60) but not girls. There also was an association between 1-mg higher daily intake of maternal fluoride intake and decreased IQ score in both boys and girls (−3.66; 95% CI, −7.16 to −0.15 ; P = .04).
Ms. Green and her colleagues acknowledged several limitations with the study, such as the short half-life of urinary fluoride and the potential inaccuracy of maternal urinary samples at predicting fetal exposure to fluoride, the self-reported nature of estimated fluoride consumption, lack of availability of maternal IQ data, and not including postnatal exposure and consumption of fluoride.
In a related editorial, David C. Bellinger, PhD, MSc, referred to a previous prospective study in Mexico City by Bashash et al. that found a maternal fluoride level of 0.9 mg/L was associated with a decrease in cognitive scores in children at 4 years and between 6 years and 12 years (Environ Health Perspect. 2017;125(9):097017. doi: 10.1289/EHP655), and noted the effect sizes seen in the Mexico City study were similar to those reported by Green et al. “If the effect sizes reported by Green et al. and others are valid, the total cognitive loss at the population level that might be associated with children’s prenatal exposure to fluoride could be substantial,” he said.
The study raises many questions, including whether there is a concentration where neurotoxicity risk is negligible, if gender plays a role (there was no gender risk difference in Bashash et al.), whether other developmental domains are affected apart from IQ, and if postnatal exposure carries a risk, Dr. Bellinger said. “The findings of Green et al. and others indicate that a dispassionate and tempered discussion of fluoride’s potential neurotoxicity is warranted, including consideration of what additional research is needed to reach more definitive conclusions about the implications, if any, for public health,” he said.
Dimitri A. Christakis, MD, MPH, editor of JAMA Pediatrics and director of the Center for Child Health, Behavior, and Development at Seattle Children’s Research Institute, said in an editor’s note that it was not an easy decision to publish the article because of the potential implications of the findings.
“The mission of the journal is to ensure that child health is optimized by bringing the best available evidence to the fore,” he said. “Publishing it serves as testament to the fact that JAMA Pediatrics is committed to disseminating the best science based entirely on the rigor of the methods and the soundness of the hypotheses tested, regardless of how contentious the results may be.”
However, “scientific inquiry is an iterative process,” Dr. Christakis said, and rarely does a single study provide “definitive evidence.
“We hope that purveyors and consumers of these findings are mindful of that as the implications of this study are debated in the public arena.”
This study was funded in a grant from the National Institute of Environmental Health Science, and the MIREC Study was funded by Chemicals Management Plan at Health Canada, the Ontario Ministry of the Environment, and the Canadian Institutes for Health Research. Dr. Bruce Lanphear reported being an unpaid expert witness for an upcoming case involving the U.S. Environmental Protection Agency and water fluoridation. Dr. Richard Hornung reported receiving personal fees from York University. Dr. E. Angeles Martinez-Mier reported receiving grants from the National Institutes of Health. The other authors report no relevant conflicts of interest. Dr. Bellinger reported no relevant conflicts of interest with regard to his editorial.
SOURCEs: Green R et al. JAMA Pediatr. 2019. doi: 10.1001/jamapediatrics.2019.1729; Bellinger. JAMA Pediatr. 2019. doi: 10.1001/ jamapediatrics.2019.1728.
with boys having a lower mean score than girls, according to a recent prospective, multicenter birth cohort study.
“These findings were observed at fluoride levels typically found in white North American women,” wrote Rivka Green, York University, Toronto, and colleagues. “This indicates the possible need to reduce fluoride intake during pregnancy.”
This study confirms findings in a 2017 study suggesting a relationship between maternal fluoride levels and children’s later cognitive scores.
Ms. Green and colleagues evaluated 512 mother-child pairs in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort from six Canadian cities. The children were born between 2008 and 2012, underwent neurodevelopmental testing between 3 and 4 years, and were assessed using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. Full Scale IQ (FSIQ) test.
Of these, 400 mother-child pairs had data on fluoride intake, IQ, and complete covariate data; 141 of these mothers lived in areas with fluoridated tap water, while 228 mothers lived in areas without fluoridated tap water. Maternal urinary fluoride adjusted for specific gravity (MUFSG) was averaged across three trimesters of data, and the estimated fluoride level was obtained through self-reported exposure by women included in the study.
The researchers found mothers living in areas with fluoridated water had significantly higher MUFSG levels (0.69 mg/L), compared with women in areas without fluoridated water (0.40 mg/L; P equals .001). The median estimated fluoride intake was significantly higher among women living in areas with fluoridated water (0.93 mg per day) than in women who did not live in areas with fluoridated water (0.30 mg per day; P less than .001).
Overall, children scored a mean 107.16 (range, 52-143) on the IQ test, and girls had significantly higher mean IQ scores than did boys (109.56 vs. 104.61; P = .001). After adjusting for covariates of maternal age, race, parity, smoking, and alcohol status during pregnancy, child gender, gestational age, and birth weight, the researchers found a significant interaction between MUFSG and the child’s gender (P = .02), and a 1-mg/L MUFSG increase was associated with a decrease in 4.49 IQ points in boys (95% confidence interval, −8.38 to −0.60) but not girls. There also was an association between 1-mg higher daily intake of maternal fluoride intake and decreased IQ score in both boys and girls (−3.66; 95% CI, −7.16 to −0.15 ; P = .04).
Ms. Green and her colleagues acknowledged several limitations with the study, such as the short half-life of urinary fluoride and the potential inaccuracy of maternal urinary samples at predicting fetal exposure to fluoride, the self-reported nature of estimated fluoride consumption, lack of availability of maternal IQ data, and not including postnatal exposure and consumption of fluoride.
In a related editorial, David C. Bellinger, PhD, MSc, referred to a previous prospective study in Mexico City by Bashash et al. that found a maternal fluoride level of 0.9 mg/L was associated with a decrease in cognitive scores in children at 4 years and between 6 years and 12 years (Environ Health Perspect. 2017;125(9):097017. doi: 10.1289/EHP655), and noted the effect sizes seen in the Mexico City study were similar to those reported by Green et al. “If the effect sizes reported by Green et al. and others are valid, the total cognitive loss at the population level that might be associated with children’s prenatal exposure to fluoride could be substantial,” he said.
The study raises many questions, including whether there is a concentration where neurotoxicity risk is negligible, if gender plays a role (there was no gender risk difference in Bashash et al.), whether other developmental domains are affected apart from IQ, and if postnatal exposure carries a risk, Dr. Bellinger said. “The findings of Green et al. and others indicate that a dispassionate and tempered discussion of fluoride’s potential neurotoxicity is warranted, including consideration of what additional research is needed to reach more definitive conclusions about the implications, if any, for public health,” he said.
Dimitri A. Christakis, MD, MPH, editor of JAMA Pediatrics and director of the Center for Child Health, Behavior, and Development at Seattle Children’s Research Institute, said in an editor’s note that it was not an easy decision to publish the article because of the potential implications of the findings.
“The mission of the journal is to ensure that child health is optimized by bringing the best available evidence to the fore,” he said. “Publishing it serves as testament to the fact that JAMA Pediatrics is committed to disseminating the best science based entirely on the rigor of the methods and the soundness of the hypotheses tested, regardless of how contentious the results may be.”
However, “scientific inquiry is an iterative process,” Dr. Christakis said, and rarely does a single study provide “definitive evidence.
“We hope that purveyors and consumers of these findings are mindful of that as the implications of this study are debated in the public arena.”
This study was funded in a grant from the National Institute of Environmental Health Science, and the MIREC Study was funded by Chemicals Management Plan at Health Canada, the Ontario Ministry of the Environment, and the Canadian Institutes for Health Research. Dr. Bruce Lanphear reported being an unpaid expert witness for an upcoming case involving the U.S. Environmental Protection Agency and water fluoridation. Dr. Richard Hornung reported receiving personal fees from York University. Dr. E. Angeles Martinez-Mier reported receiving grants from the National Institutes of Health. The other authors report no relevant conflicts of interest. Dr. Bellinger reported no relevant conflicts of interest with regard to his editorial.
SOURCEs: Green R et al. JAMA Pediatr. 2019. doi: 10.1001/jamapediatrics.2019.1729; Bellinger. JAMA Pediatr. 2019. doi: 10.1001/ jamapediatrics.2019.1728.
FROM JAMA PEDIATRICS
Differential monocytic HLA-DR expression prognostically useful in PICU
LJUBLJANA, SLOVENIA – During their first 4 days in the pediatric ICU, critically ill children have significantly reduced human leukocyte antigen (HLA)–DR expression within all three major subsets of monocytes. The reductions are seen regardless of whether the children were admitted for sepsis, trauma, or after surgery, Navin Boeddha, MD, PhD, reported in his PIDJ Award Lecture at the annual meeting of the European Society for Paediatric Infectious Diseases.
The PIDJ Award is given annually by the editors of the Pediatric Infectious Disease Journal in recognition of what they deem the most important study published in the journal during the prior year. This one stood out because it identified promising potential laboratory markers that have been sought as a prerequisite to developing immunostimulatory therapies aimed at improving outcomes in severely immunosuppressed children.
Researchers are particularly eager to explore this investigative treatment strategy because the mortality and long-term morbidity of pediatric sepsis, in particular, remain unacceptably high. The hope now is that HLA-DR expression on monocyte subsets will be helpful in directing granulocyte-macrophage colony-stimulating factor, interferon-gamma, and other immunostimulatory therapies to the pediatric ICU patients with the most favorable benefit/risk ratio, according to Dr. Boeddha of Sophia Children’s Hospital and Erasmus University, Rotterdam, the Netherlands.
He reported on 37 critically ill children admitted to a pediatric ICU – 12 for sepsis, 11 post surgery, 10 for trauma, and 4 for other reasons – as well as 37 healthy controls. HLA-DR expression on monocyte subsets was measured by flow cytometry upon admission and again on each of the following 3 days.
The impetus for this study is that severe infection, major surgery, and severe trauma are often associated with immunosuppression. And while prior work in septic adults has concluded that decreased monocytic HLA-DR expression is a marker for immunosuppression – and that the lower the level of such expression, the greater the risk of nosocomial infection and death – this phenomenon hasn’t been well studied in critically ill children, he explained.
Dr. Boeddha and coinvestigators found that monocytic HLA-DR expression, which plays a major role in presenting antigens to T cells, decreased over time during the critically ill children’s first 4 days in the pediatric ICU. Moreover, it was lower than in controls at all four time points. This was true both for the percentage of HLA-DR–expressing monocytes of all subsets, as well as for HLA-DR mean fluorescence intensity.
In the critically ill study population as a whole, the percentage of classical monocytes – that is, CD14++ CD16– monocytes – was significantly greater at admission than in healthy controls by margins of 95% and 87%, while the percentage of nonclassical CD14+/-CD16++ monocytes was markedly lower at 2% than the 9% figure in controls.
The biggest discrepancy in monocyte subset distribution was seen in patients admitted for sepsis. Their percentage of classical monocytes was lower than in controls by a margin of 82% versus 87%; however, their proportion of intermediate monocytes (CD14++ CD16+) upon admission was twice that of controls, and it climbed further to 14% on day 2.
Among the key findings in the Rotterdam study: 13 of 37 critically ill patients experienced at least one nosocomial infection while in the pediatric ICU. Their day 2 percentage of HLA-DR–expressing classical monocytes was 42%, strikingly lower than the 78% figure in patients who didn’t develop an infection. Also, the 6 patients who died had only a 33% rate of HLA-DR–expressing classical monocytes on day 3 after pediatric ICU admission versus a 63% rate in survivors of their critical illness.
Thus, low HLA-DR expression on classical monocytes early during the course of a pediatric ICU stay may be the sought-after biomarker that identifies a particularly high-risk subgroup of critically ill children in whom immunostimulatory therapies should be studied. However, future confirmatory studies should monitor monocytic HLA-DR expression in a larger critically ill patient population for a longer period in order to establish the time to recovery of low expression and its impact on long-term complications, the physician said.
Dr. Boeddha reported having no financial conflicts regarding the award-winning study, supported by the European Union and Erasmus University.
SOURCE: Boeddha NP et al. Pediatr Infect Dis J. 2018 Oct;37(10):1034-40.
LJUBLJANA, SLOVENIA – During their first 4 days in the pediatric ICU, critically ill children have significantly reduced human leukocyte antigen (HLA)–DR expression within all three major subsets of monocytes. The reductions are seen regardless of whether the children were admitted for sepsis, trauma, or after surgery, Navin Boeddha, MD, PhD, reported in his PIDJ Award Lecture at the annual meeting of the European Society for Paediatric Infectious Diseases.
The PIDJ Award is given annually by the editors of the Pediatric Infectious Disease Journal in recognition of what they deem the most important study published in the journal during the prior year. This one stood out because it identified promising potential laboratory markers that have been sought as a prerequisite to developing immunostimulatory therapies aimed at improving outcomes in severely immunosuppressed children.
Researchers are particularly eager to explore this investigative treatment strategy because the mortality and long-term morbidity of pediatric sepsis, in particular, remain unacceptably high. The hope now is that HLA-DR expression on monocyte subsets will be helpful in directing granulocyte-macrophage colony-stimulating factor, interferon-gamma, and other immunostimulatory therapies to the pediatric ICU patients with the most favorable benefit/risk ratio, according to Dr. Boeddha of Sophia Children’s Hospital and Erasmus University, Rotterdam, the Netherlands.
He reported on 37 critically ill children admitted to a pediatric ICU – 12 for sepsis, 11 post surgery, 10 for trauma, and 4 for other reasons – as well as 37 healthy controls. HLA-DR expression on monocyte subsets was measured by flow cytometry upon admission and again on each of the following 3 days.
The impetus for this study is that severe infection, major surgery, and severe trauma are often associated with immunosuppression. And while prior work in septic adults has concluded that decreased monocytic HLA-DR expression is a marker for immunosuppression – and that the lower the level of such expression, the greater the risk of nosocomial infection and death – this phenomenon hasn’t been well studied in critically ill children, he explained.
Dr. Boeddha and coinvestigators found that monocytic HLA-DR expression, which plays a major role in presenting antigens to T cells, decreased over time during the critically ill children’s first 4 days in the pediatric ICU. Moreover, it was lower than in controls at all four time points. This was true both for the percentage of HLA-DR–expressing monocytes of all subsets, as well as for HLA-DR mean fluorescence intensity.
In the critically ill study population as a whole, the percentage of classical monocytes – that is, CD14++ CD16– monocytes – was significantly greater at admission than in healthy controls by margins of 95% and 87%, while the percentage of nonclassical CD14+/-CD16++ monocytes was markedly lower at 2% than the 9% figure in controls.
The biggest discrepancy in monocyte subset distribution was seen in patients admitted for sepsis. Their percentage of classical monocytes was lower than in controls by a margin of 82% versus 87%; however, their proportion of intermediate monocytes (CD14++ CD16+) upon admission was twice that of controls, and it climbed further to 14% on day 2.
Among the key findings in the Rotterdam study: 13 of 37 critically ill patients experienced at least one nosocomial infection while in the pediatric ICU. Their day 2 percentage of HLA-DR–expressing classical monocytes was 42%, strikingly lower than the 78% figure in patients who didn’t develop an infection. Also, the 6 patients who died had only a 33% rate of HLA-DR–expressing classical monocytes on day 3 after pediatric ICU admission versus a 63% rate in survivors of their critical illness.
Thus, low HLA-DR expression on classical monocytes early during the course of a pediatric ICU stay may be the sought-after biomarker that identifies a particularly high-risk subgroup of critically ill children in whom immunostimulatory therapies should be studied. However, future confirmatory studies should monitor monocytic HLA-DR expression in a larger critically ill patient population for a longer period in order to establish the time to recovery of low expression and its impact on long-term complications, the physician said.
Dr. Boeddha reported having no financial conflicts regarding the award-winning study, supported by the European Union and Erasmus University.
SOURCE: Boeddha NP et al. Pediatr Infect Dis J. 2018 Oct;37(10):1034-40.
LJUBLJANA, SLOVENIA – During their first 4 days in the pediatric ICU, critically ill children have significantly reduced human leukocyte antigen (HLA)–DR expression within all three major subsets of monocytes. The reductions are seen regardless of whether the children were admitted for sepsis, trauma, or after surgery, Navin Boeddha, MD, PhD, reported in his PIDJ Award Lecture at the annual meeting of the European Society for Paediatric Infectious Diseases.
The PIDJ Award is given annually by the editors of the Pediatric Infectious Disease Journal in recognition of what they deem the most important study published in the journal during the prior year. This one stood out because it identified promising potential laboratory markers that have been sought as a prerequisite to developing immunostimulatory therapies aimed at improving outcomes in severely immunosuppressed children.
Researchers are particularly eager to explore this investigative treatment strategy because the mortality and long-term morbidity of pediatric sepsis, in particular, remain unacceptably high. The hope now is that HLA-DR expression on monocyte subsets will be helpful in directing granulocyte-macrophage colony-stimulating factor, interferon-gamma, and other immunostimulatory therapies to the pediatric ICU patients with the most favorable benefit/risk ratio, according to Dr. Boeddha of Sophia Children’s Hospital and Erasmus University, Rotterdam, the Netherlands.
He reported on 37 critically ill children admitted to a pediatric ICU – 12 for sepsis, 11 post surgery, 10 for trauma, and 4 for other reasons – as well as 37 healthy controls. HLA-DR expression on monocyte subsets was measured by flow cytometry upon admission and again on each of the following 3 days.
The impetus for this study is that severe infection, major surgery, and severe trauma are often associated with immunosuppression. And while prior work in septic adults has concluded that decreased monocytic HLA-DR expression is a marker for immunosuppression – and that the lower the level of such expression, the greater the risk of nosocomial infection and death – this phenomenon hasn’t been well studied in critically ill children, he explained.
Dr. Boeddha and coinvestigators found that monocytic HLA-DR expression, which plays a major role in presenting antigens to T cells, decreased over time during the critically ill children’s first 4 days in the pediatric ICU. Moreover, it was lower than in controls at all four time points. This was true both for the percentage of HLA-DR–expressing monocytes of all subsets, as well as for HLA-DR mean fluorescence intensity.
In the critically ill study population as a whole, the percentage of classical monocytes – that is, CD14++ CD16– monocytes – was significantly greater at admission than in healthy controls by margins of 95% and 87%, while the percentage of nonclassical CD14+/-CD16++ monocytes was markedly lower at 2% than the 9% figure in controls.
The biggest discrepancy in monocyte subset distribution was seen in patients admitted for sepsis. Their percentage of classical monocytes was lower than in controls by a margin of 82% versus 87%; however, their proportion of intermediate monocytes (CD14++ CD16+) upon admission was twice that of controls, and it climbed further to 14% on day 2.
Among the key findings in the Rotterdam study: 13 of 37 critically ill patients experienced at least one nosocomial infection while in the pediatric ICU. Their day 2 percentage of HLA-DR–expressing classical monocytes was 42%, strikingly lower than the 78% figure in patients who didn’t develop an infection. Also, the 6 patients who died had only a 33% rate of HLA-DR–expressing classical monocytes on day 3 after pediatric ICU admission versus a 63% rate in survivors of their critical illness.
Thus, low HLA-DR expression on classical monocytes early during the course of a pediatric ICU stay may be the sought-after biomarker that identifies a particularly high-risk subgroup of critically ill children in whom immunostimulatory therapies should be studied. However, future confirmatory studies should monitor monocytic HLA-DR expression in a larger critically ill patient population for a longer period in order to establish the time to recovery of low expression and its impact on long-term complications, the physician said.
Dr. Boeddha reported having no financial conflicts regarding the award-winning study, supported by the European Union and Erasmus University.
SOURCE: Boeddha NP et al. Pediatr Infect Dis J. 2018 Oct;37(10):1034-40.
REPORTING FROM ESPID 2019
Presepsin can rule out invasive bacterial infection in infants
LJUBLJANA, SLOVENIA – A point-of-care presepsin measurement in the emergency department displayed powerful accuracy for early rule-out of invasive bacterial infection in infants less than 3 months old presenting with fever without a source, based on results of a phase 3 multicenter Italian study.
“P-SEP [presepsin] is a promising new biomarker. P-SEP accuracy for invasive bacterial infection is comparable to procalcitonin, even though P-SEP, like procalcitonin, is probably not accurate enough to be used as a stand-alone marker to rule-in an invasive bacterial infection,” Luca Pierantoni, MD, said in presenting the preliminary study results at the annual meeting of the European Society for Paediatric Infectious Diseases.
The presepsin test is a rapid point-of-care test well-suited for the ED setting, with a cost equal to that of point-of-care procalcitonin.
Presepsin is a form of soluble CD14 that is released from the surface of macrophages, monocytes, and neutrophils when these immune cells are stimulated by pathogens. “We think it may be a reliable diagnostic and prognostic marker of sepsis in adults and neonates,” explained Dr. Pierantoni of the University of Bologna, Italy.
Indeed, studies in adults suggest presepsin has better sensitivity and specificity than other biomarkers for early diagnosis of sepsis, and that it provides useful information on severity and prognosis as well. But, Dr. Pierantoni and his coworkers wondered, how does it perform in febrile young infants?
The Italian study was designed to address an unmet need: Fever accounts for about one-third of ED visits in infants up to age 3 months, 20% of whom are initially categorized as having fever without source. Yet ultimately 10%-20% of those youngsters having fever without source are found to have an invasive bacterial infection – that is, sepsis or meningitis – or a severe bacterial infection such as pneumonia, a urinary tract infection, or an infected umbilical cord. The sooner these infants can be identified and appropriately treated, the better.
The study enrolled 284 children less than 3 months old who had fever without cause of a mean 10.5 hours duration and presented to the emergency departments of six Italian medical centers. Children were eligible for the study regardless of whether they appeared toxic or well. Presepsin, procalcitonin, and C-reactive protein levels were immediately measured in all participants. Ultimately, 5.6% of subjects were diagnosed with an invasive bacterial infection, and another 21.2% had a severe bacterial infection.
Using a cutoff value of 449 pg/mL, P-SEP had good diagnostic accuracy for invasive bacterial infection, with an area under the receiver operating characteristics curve of 0.81, essentially the same as the 0.82 value for procalcitonin. P-SEP had a sensitivity and specificity of 87% and 75%, respectively, placing it in the same ballpark as the 82% and 86% values for procalcitonin. The strong point for P-SEP was its 99% negative predictive value, as compared to 91% for procalcitonin. The positive predictive values were 17% for P-SEP and 20% for procalcitonin.
In response to an audience question, Dr. Pierantoni speculated that the best use for P-SEP in the setting of fever of unknown origin may be in combination with procalcitonin rather than as a replacement for it. The research team is now in the process of analyzing their study data to see if that is indeed the case.
He reported having no financial conflicts regarding his study, conducted free of commercial support.
LJUBLJANA, SLOVENIA – A point-of-care presepsin measurement in the emergency department displayed powerful accuracy for early rule-out of invasive bacterial infection in infants less than 3 months old presenting with fever without a source, based on results of a phase 3 multicenter Italian study.
“P-SEP [presepsin] is a promising new biomarker. P-SEP accuracy for invasive bacterial infection is comparable to procalcitonin, even though P-SEP, like procalcitonin, is probably not accurate enough to be used as a stand-alone marker to rule-in an invasive bacterial infection,” Luca Pierantoni, MD, said in presenting the preliminary study results at the annual meeting of the European Society for Paediatric Infectious Diseases.
The presepsin test is a rapid point-of-care test well-suited for the ED setting, with a cost equal to that of point-of-care procalcitonin.
Presepsin is a form of soluble CD14 that is released from the surface of macrophages, monocytes, and neutrophils when these immune cells are stimulated by pathogens. “We think it may be a reliable diagnostic and prognostic marker of sepsis in adults and neonates,” explained Dr. Pierantoni of the University of Bologna, Italy.
Indeed, studies in adults suggest presepsin has better sensitivity and specificity than other biomarkers for early diagnosis of sepsis, and that it provides useful information on severity and prognosis as well. But, Dr. Pierantoni and his coworkers wondered, how does it perform in febrile young infants?
The Italian study was designed to address an unmet need: Fever accounts for about one-third of ED visits in infants up to age 3 months, 20% of whom are initially categorized as having fever without source. Yet ultimately 10%-20% of those youngsters having fever without source are found to have an invasive bacterial infection – that is, sepsis or meningitis – or a severe bacterial infection such as pneumonia, a urinary tract infection, or an infected umbilical cord. The sooner these infants can be identified and appropriately treated, the better.
The study enrolled 284 children less than 3 months old who had fever without cause of a mean 10.5 hours duration and presented to the emergency departments of six Italian medical centers. Children were eligible for the study regardless of whether they appeared toxic or well. Presepsin, procalcitonin, and C-reactive protein levels were immediately measured in all participants. Ultimately, 5.6% of subjects were diagnosed with an invasive bacterial infection, and another 21.2% had a severe bacterial infection.
Using a cutoff value of 449 pg/mL, P-SEP had good diagnostic accuracy for invasive bacterial infection, with an area under the receiver operating characteristics curve of 0.81, essentially the same as the 0.82 value for procalcitonin. P-SEP had a sensitivity and specificity of 87% and 75%, respectively, placing it in the same ballpark as the 82% and 86% values for procalcitonin. The strong point for P-SEP was its 99% negative predictive value, as compared to 91% for procalcitonin. The positive predictive values were 17% for P-SEP and 20% for procalcitonin.
In response to an audience question, Dr. Pierantoni speculated that the best use for P-SEP in the setting of fever of unknown origin may be in combination with procalcitonin rather than as a replacement for it. The research team is now in the process of analyzing their study data to see if that is indeed the case.
He reported having no financial conflicts regarding his study, conducted free of commercial support.
LJUBLJANA, SLOVENIA – A point-of-care presepsin measurement in the emergency department displayed powerful accuracy for early rule-out of invasive bacterial infection in infants less than 3 months old presenting with fever without a source, based on results of a phase 3 multicenter Italian study.
“P-SEP [presepsin] is a promising new biomarker. P-SEP accuracy for invasive bacterial infection is comparable to procalcitonin, even though P-SEP, like procalcitonin, is probably not accurate enough to be used as a stand-alone marker to rule-in an invasive bacterial infection,” Luca Pierantoni, MD, said in presenting the preliminary study results at the annual meeting of the European Society for Paediatric Infectious Diseases.
The presepsin test is a rapid point-of-care test well-suited for the ED setting, with a cost equal to that of point-of-care procalcitonin.
Presepsin is a form of soluble CD14 that is released from the surface of macrophages, monocytes, and neutrophils when these immune cells are stimulated by pathogens. “We think it may be a reliable diagnostic and prognostic marker of sepsis in adults and neonates,” explained Dr. Pierantoni of the University of Bologna, Italy.
Indeed, studies in adults suggest presepsin has better sensitivity and specificity than other biomarkers for early diagnosis of sepsis, and that it provides useful information on severity and prognosis as well. But, Dr. Pierantoni and his coworkers wondered, how does it perform in febrile young infants?
The Italian study was designed to address an unmet need: Fever accounts for about one-third of ED visits in infants up to age 3 months, 20% of whom are initially categorized as having fever without source. Yet ultimately 10%-20% of those youngsters having fever without source are found to have an invasive bacterial infection – that is, sepsis or meningitis – or a severe bacterial infection such as pneumonia, a urinary tract infection, or an infected umbilical cord. The sooner these infants can be identified and appropriately treated, the better.
The study enrolled 284 children less than 3 months old who had fever without cause of a mean 10.5 hours duration and presented to the emergency departments of six Italian medical centers. Children were eligible for the study regardless of whether they appeared toxic or well. Presepsin, procalcitonin, and C-reactive protein levels were immediately measured in all participants. Ultimately, 5.6% of subjects were diagnosed with an invasive bacterial infection, and another 21.2% had a severe bacterial infection.
Using a cutoff value of 449 pg/mL, P-SEP had good diagnostic accuracy for invasive bacterial infection, with an area under the receiver operating characteristics curve of 0.81, essentially the same as the 0.82 value for procalcitonin. P-SEP had a sensitivity and specificity of 87% and 75%, respectively, placing it in the same ballpark as the 82% and 86% values for procalcitonin. The strong point for P-SEP was its 99% negative predictive value, as compared to 91% for procalcitonin. The positive predictive values were 17% for P-SEP and 20% for procalcitonin.
In response to an audience question, Dr. Pierantoni speculated that the best use for P-SEP in the setting of fever of unknown origin may be in combination with procalcitonin rather than as a replacement for it. The research team is now in the process of analyzing their study data to see if that is indeed the case.
He reported having no financial conflicts regarding his study, conducted free of commercial support.
REPORTING FROM ESPID 2019
Key clinical point: A rapid point-of-care measurement of presepsin in the ED can rule out invasive bacterial infection with 99% accuracy in young infants with fever of unknown source.
Major finding: The negative predictive value of a presepsin level below the cutoff value of 449 pg/mL was 99%.
Study details: This was a multicenter Italian observational study of 284 infants less than 3 months old who presented to emergency departments with fever without source.
Disclosures: The presenter reported having no financial conflicts regarding his study, conducted free of commercial support.
Pediatric, adolescent migraine treatment and prevention guidelines are updated
Two new guidelines on the treatment and prevention of migraines in children and adolescents have been released by the American Academy of Neurology and the American Headache Society.
This update to the previous guidelines released by the American Academy of Neurology in 2004 reflects the expansion in pharmacologic and nonpharmacologic approaches during the last 15 years, Andrew D. Hershey, MD, PhD, director of the division of neurology at Cincinnati Children’s Hospital and a fellow of the American Academy of Neurology, said in an interview.
“There has also been an increase in the number of randomized controlled studies, which have allowed for a more robust statement on acute and preventive treatments to be made,” said Dr. Hershey, who is also a senior author for both guidelines.
The two reports focused on separate issues: One guideline outlined the options for treatment of acute migraine, and the second guideline summarized the available studies on the effectiveness of preventive medications for migraine in children and adolescents.
The guidelines recommend a physical examination and history to establish a specific headache diagnosis and afford a treatment that provides fast and complete pain relief. Treatment should be initiated as soon as a patient realizes an attack is occurring. Patients with signs of secondary headache should be evaluated by a neurologist or a headache specialist.
Studies support the use of ibuprofen and acetaminophen for pain relief in cases of acute migraine, but only some triptans (such as almotriptan, rizatriptan, sumatriptan/naproxen, and zolmitriptan nasal spray) are approved for use in adolescents. Specifically, sumatriptan/naproxen was shown to be effective when compared with placebo in studies with adolescents, whose headache symptoms resolved within 2 hours.
It may be necessary to try more than one triptan, the guidelines noted, because patients respond differently to medications. A failure to respond to one triptan does not necessarily mean that treatment with another triptan will be unsuccessful.
The guidelines also focused on patient and family education to improve medication safety and adherence. Lifestyle modification, avoidance of migraine triggers, creating good sleep habits, and staying hydrated can help reduce migraines. While no medications improved associated symptoms of migraines such as nausea or vomiting, triptans did show a benefit in reducing phonophobia and photophobia.
Evidence for pharmacologic prevention of migraines in children and adolescents is limited, according to the guidelines. In the 15 studies included in a literature review, there was not sufficient evidence to show preventive treatments, such as divalproex, onabotulinumtoxinA, amitriptyline, nimodipine, and flunarizine, were more effective than placebo at reducing the frequency of headaches. There was some evidence to show propranolol in children and topiramate and cinnarizine in children and adolescents can reduce headache frequency. Children and adolescents who received cognitive-behavioral therapy together with amitriptyline were more likely to have reduced frequency of headaches than were those who received amitriptyline with patient education.
“The consensus conclusion was that a multidisciplinary approach that combines acute treatments, preventive treatments, and healthy habits is likely to have the best outcomes,” said Dr. Hershey.
Dr. Hershey acknowledged the many gaps between what is clinically observed and what the studies in the guidelines demonstrated.
“One of the biggest questions is how to minimize the expectation response in the controlled studies,” he said. “Additionally, we are moving toward a better recognition of the mechanism by which the various treatments work in a genetic-based disease that is polygenic in nature” with up to 38 different gene polymorphisms identified to date.
The guidelines also do not address newer treatments, such as calcitonin gene–related peptide (CGRP) antibodies, CGRP antagonists, serotonin antagonists, and devices because there are as yet no studies of their effectiveness in children and adolescents.
“They have been studied in adults, so will be prone to the expectation response; but given the large number of diverse therapies, one can hope that many of the gaps can be filled,” said Dr. Hershey.
The American Academy of Neurology provided funding for development of the guidelines and reimbursed authors who served as subcommittee members for travel expenses and in-person meetings. The authors reported personal and institutional relationships in the form of advisory board memberships, investigator appointments, speakers bureau positions, research support, grants, honorariums, consultancies, and publishing royalties for pharmaceutical companies and other organizations.
SOURCES: Oskoui M et al. Neurology. 2019 Aug 14. doi: 10.1212/WNL.0000000000008095. Oskoui M et al. Neurology. 2019 Aug 14. doi: 10.1212/WNL.0000000000008105.
Two new guidelines on the treatment and prevention of migraines in children and adolescents have been released by the American Academy of Neurology and the American Headache Society.
This update to the previous guidelines released by the American Academy of Neurology in 2004 reflects the expansion in pharmacologic and nonpharmacologic approaches during the last 15 years, Andrew D. Hershey, MD, PhD, director of the division of neurology at Cincinnati Children’s Hospital and a fellow of the American Academy of Neurology, said in an interview.
“There has also been an increase in the number of randomized controlled studies, which have allowed for a more robust statement on acute and preventive treatments to be made,” said Dr. Hershey, who is also a senior author for both guidelines.
The two reports focused on separate issues: One guideline outlined the options for treatment of acute migraine, and the second guideline summarized the available studies on the effectiveness of preventive medications for migraine in children and adolescents.
The guidelines recommend a physical examination and history to establish a specific headache diagnosis and afford a treatment that provides fast and complete pain relief. Treatment should be initiated as soon as a patient realizes an attack is occurring. Patients with signs of secondary headache should be evaluated by a neurologist or a headache specialist.
Studies support the use of ibuprofen and acetaminophen for pain relief in cases of acute migraine, but only some triptans (such as almotriptan, rizatriptan, sumatriptan/naproxen, and zolmitriptan nasal spray) are approved for use in adolescents. Specifically, sumatriptan/naproxen was shown to be effective when compared with placebo in studies with adolescents, whose headache symptoms resolved within 2 hours.
It may be necessary to try more than one triptan, the guidelines noted, because patients respond differently to medications. A failure to respond to one triptan does not necessarily mean that treatment with another triptan will be unsuccessful.
The guidelines also focused on patient and family education to improve medication safety and adherence. Lifestyle modification, avoidance of migraine triggers, creating good sleep habits, and staying hydrated can help reduce migraines. While no medications improved associated symptoms of migraines such as nausea or vomiting, triptans did show a benefit in reducing phonophobia and photophobia.
Evidence for pharmacologic prevention of migraines in children and adolescents is limited, according to the guidelines. In the 15 studies included in a literature review, there was not sufficient evidence to show preventive treatments, such as divalproex, onabotulinumtoxinA, amitriptyline, nimodipine, and flunarizine, were more effective than placebo at reducing the frequency of headaches. There was some evidence to show propranolol in children and topiramate and cinnarizine in children and adolescents can reduce headache frequency. Children and adolescents who received cognitive-behavioral therapy together with amitriptyline were more likely to have reduced frequency of headaches than were those who received amitriptyline with patient education.
“The consensus conclusion was that a multidisciplinary approach that combines acute treatments, preventive treatments, and healthy habits is likely to have the best outcomes,” said Dr. Hershey.
Dr. Hershey acknowledged the many gaps between what is clinically observed and what the studies in the guidelines demonstrated.
“One of the biggest questions is how to minimize the expectation response in the controlled studies,” he said. “Additionally, we are moving toward a better recognition of the mechanism by which the various treatments work in a genetic-based disease that is polygenic in nature” with up to 38 different gene polymorphisms identified to date.
The guidelines also do not address newer treatments, such as calcitonin gene–related peptide (CGRP) antibodies, CGRP antagonists, serotonin antagonists, and devices because there are as yet no studies of their effectiveness in children and adolescents.
“They have been studied in adults, so will be prone to the expectation response; but given the large number of diverse therapies, one can hope that many of the gaps can be filled,” said Dr. Hershey.
The American Academy of Neurology provided funding for development of the guidelines and reimbursed authors who served as subcommittee members for travel expenses and in-person meetings. The authors reported personal and institutional relationships in the form of advisory board memberships, investigator appointments, speakers bureau positions, research support, grants, honorariums, consultancies, and publishing royalties for pharmaceutical companies and other organizations.
SOURCES: Oskoui M et al. Neurology. 2019 Aug 14. doi: 10.1212/WNL.0000000000008095. Oskoui M et al. Neurology. 2019 Aug 14. doi: 10.1212/WNL.0000000000008105.
Two new guidelines on the treatment and prevention of migraines in children and adolescents have been released by the American Academy of Neurology and the American Headache Society.
This update to the previous guidelines released by the American Academy of Neurology in 2004 reflects the expansion in pharmacologic and nonpharmacologic approaches during the last 15 years, Andrew D. Hershey, MD, PhD, director of the division of neurology at Cincinnati Children’s Hospital and a fellow of the American Academy of Neurology, said in an interview.
“There has also been an increase in the number of randomized controlled studies, which have allowed for a more robust statement on acute and preventive treatments to be made,” said Dr. Hershey, who is also a senior author for both guidelines.
The two reports focused on separate issues: One guideline outlined the options for treatment of acute migraine, and the second guideline summarized the available studies on the effectiveness of preventive medications for migraine in children and adolescents.
The guidelines recommend a physical examination and history to establish a specific headache diagnosis and afford a treatment that provides fast and complete pain relief. Treatment should be initiated as soon as a patient realizes an attack is occurring. Patients with signs of secondary headache should be evaluated by a neurologist or a headache specialist.
Studies support the use of ibuprofen and acetaminophen for pain relief in cases of acute migraine, but only some triptans (such as almotriptan, rizatriptan, sumatriptan/naproxen, and zolmitriptan nasal spray) are approved for use in adolescents. Specifically, sumatriptan/naproxen was shown to be effective when compared with placebo in studies with adolescents, whose headache symptoms resolved within 2 hours.
It may be necessary to try more than one triptan, the guidelines noted, because patients respond differently to medications. A failure to respond to one triptan does not necessarily mean that treatment with another triptan will be unsuccessful.
The guidelines also focused on patient and family education to improve medication safety and adherence. Lifestyle modification, avoidance of migraine triggers, creating good sleep habits, and staying hydrated can help reduce migraines. While no medications improved associated symptoms of migraines such as nausea or vomiting, triptans did show a benefit in reducing phonophobia and photophobia.
Evidence for pharmacologic prevention of migraines in children and adolescents is limited, according to the guidelines. In the 15 studies included in a literature review, there was not sufficient evidence to show preventive treatments, such as divalproex, onabotulinumtoxinA, amitriptyline, nimodipine, and flunarizine, were more effective than placebo at reducing the frequency of headaches. There was some evidence to show propranolol in children and topiramate and cinnarizine in children and adolescents can reduce headache frequency. Children and adolescents who received cognitive-behavioral therapy together with amitriptyline were more likely to have reduced frequency of headaches than were those who received amitriptyline with patient education.
“The consensus conclusion was that a multidisciplinary approach that combines acute treatments, preventive treatments, and healthy habits is likely to have the best outcomes,” said Dr. Hershey.
Dr. Hershey acknowledged the many gaps between what is clinically observed and what the studies in the guidelines demonstrated.
“One of the biggest questions is how to minimize the expectation response in the controlled studies,” he said. “Additionally, we are moving toward a better recognition of the mechanism by which the various treatments work in a genetic-based disease that is polygenic in nature” with up to 38 different gene polymorphisms identified to date.
The guidelines also do not address newer treatments, such as calcitonin gene–related peptide (CGRP) antibodies, CGRP antagonists, serotonin antagonists, and devices because there are as yet no studies of their effectiveness in children and adolescents.
“They have been studied in adults, so will be prone to the expectation response; but given the large number of diverse therapies, one can hope that many of the gaps can be filled,” said Dr. Hershey.
The American Academy of Neurology provided funding for development of the guidelines and reimbursed authors who served as subcommittee members for travel expenses and in-person meetings. The authors reported personal and institutional relationships in the form of advisory board memberships, investigator appointments, speakers bureau positions, research support, grants, honorariums, consultancies, and publishing royalties for pharmaceutical companies and other organizations.
SOURCES: Oskoui M et al. Neurology. 2019 Aug 14. doi: 10.1212/WNL.0000000000008095. Oskoui M et al. Neurology. 2019 Aug 14. doi: 10.1212/WNL.0000000000008105.
FROM NEUROLOGY
Is your office ready for a case of measles?
It’s a typically busy Friday and the doctor is running 20 minutes behind schedule. He enters the next exam room and the sight of the patient makes him forget the apology he had prepared.
The 10 month old looks miserable. Red eyes. Snot dripping from his nose. A red rash that extends from his face and involves most of the chest, arms, and upper thighs.
“When did this start?” he asks the mother as he searches for a surgical mask in the cabinet next to the exam table.
“Two days after we returned from our vacation in France,” the worried young woman replies. “Do you think it could be measles?”
Between Jan. 1 and Aug. 8, 2019, 1,182 cases of measles had been confirmed in the United States. That’s more than three times the number of cases reported in all of 2018, and the highest number of cases reported in a single year in more than a quarter century. While 75% of the cases this year have been linked to outbreaks in New York, individuals from 30 states have been affected.
Given the widespread nature of the outbreak, With measles in particular, time is limited to deliver effective postexposure prophylaxis and prevent the spread of measles in the community, making it difficult to develop a plan on the fly.
Schedule strategically. You don’t want a patient with measles hanging out in your waiting room. According to the American Academy of Pediatrics, measures to prevent the transmission of contagious infectious agents in ambulatory facilities begin at the time the visit is scheduled. When there is measles transmission in the community, consider using a standardized script when scheduling patients that includes questions about fever, rash, other symptoms typical for measles, and possible exposures. Some offices will have procedures in place that can be adapted to care for patients with suspected measles. When a patient presents for suspected chicken pox, do you advise them to come at the end of the day to minimize exposures? Enter through a side door? Perform a car visit?
Triage promptly. Mask patients with fever and rash, move to a private room, and close the door.
Once measles is suspected, only health care personnel who are immune to measles should enter the exam room. According to the Centers for Disease Control and Prevention, presumptive evidence of measles immunity in health care providers is written documentation of vaccination with two doses of live measles or MMR vaccine administered at least 28 days apart, laboratory evidence of immunity (that is, positive measles IgG), laboratory confirmation of disease, or birth before 1957.
Even though health care providers born before 1957 are presumed to have had the disease at some point and have traditionally been considered immune, the CDC suggests that health care facilities consider giving these individuals two doses of MMR vaccine unless they have prior laboratory confirmation of disease immunity. Do you know who in your office is immune or would you need to scramble if you had an exposure?
When measles is suspected, health care personnel should wear an N-95 if they have been fit tested and the appropriate mask is available. Practically, most ambulatory offices do not stock N-95 masks and the next best choice is a regular surgical mask.
Order the recommended tests to confirm the diagnosis, but do not wait for the results to confirm the diagnosis. The CDC recommends testing serum for IgM antibodies and sending a throat or nasopharyngeal swab to look for the virus by polymerase chain reaction testing. Measles virus also is shed in the urine so collecting a urine specimen for testing may increase the chances of finding the virus. Depending on where you practice, the tests may take 3 days or more to result. Contact your local health department as soon as you consider a measles diagnosis.
Discharge patients home or transferred to a higher level of care if this is necessary as quickly as possible. Fortunately, most patients with measles do not require hospitalization. Do not send patients to the hospital simply for the purpose of laboratory testing if this can be accomplished quickly in your office or for evaluation by other providers. This just creates the potential for more exposures. If a patient does require higher-level care, provider-to-provider communication about the suspected diagnosis and the need for airborne isolation should take place.
Keep the door closed. Once a patient with suspected measles is discharged from a regular exam room, the door should remain closed, and it should not be used for at least 1 hour. Remember that infectious virus can remain in the air for 1-2 hours after a patient leaves an area. The same is true for the waiting room.
Develop the exposure list. In general, patients and family members who were in the waiting room at the same time as the index patient and up to 1-2 hours after the index patient left are considered exposed. Measles is highly contagious and 9 out of 10 susceptible people who are exposed will develop disease. How many infants aged less than 1 year might be in your waiting room at any given time? How many immunocompromised patients or family members? Public health authorities can help determine who needs prophylaxis.
Don’t get anxious and start testing everyone for measles, especially patients who lack typical signs and symptoms or exposures. Ordering a test in a patient who has a low likelihood of measles is more likely to result in a false-positive test than a true-positive test. False-positive measles IgM tests can be seen with some viral infections, including parvovirus and Epstein-Barr. Some rheumatologic disorders also can contribute to false-positive tests.
Review your office procedure for vaccine counseling. The 10 month old with measles in the opening vignette should have been given an MMR vaccine before travel. The vaccine is recommended for infants aged 6-11 months who are traveling outside the United States, but it doesn’t count toward the vaccine series. Reimmunize young travelers at 12-15 months and again at 4-6 years. The CDC has developed a toolkit that contains resources for taking to parents about vaccines. It is available at https://www.cdc.gov/measles/toolkit/healthcare-providers.html.
It’s a typically busy Friday and the doctor is running 20 minutes behind schedule. He enters the next exam room and the sight of the patient makes him forget the apology he had prepared.
The 10 month old looks miserable. Red eyes. Snot dripping from his nose. A red rash that extends from his face and involves most of the chest, arms, and upper thighs.
“When did this start?” he asks the mother as he searches for a surgical mask in the cabinet next to the exam table.
“Two days after we returned from our vacation in France,” the worried young woman replies. “Do you think it could be measles?”
Between Jan. 1 and Aug. 8, 2019, 1,182 cases of measles had been confirmed in the United States. That’s more than three times the number of cases reported in all of 2018, and the highest number of cases reported in a single year in more than a quarter century. While 75% of the cases this year have been linked to outbreaks in New York, individuals from 30 states have been affected.
Given the widespread nature of the outbreak, With measles in particular, time is limited to deliver effective postexposure prophylaxis and prevent the spread of measles in the community, making it difficult to develop a plan on the fly.
Schedule strategically. You don’t want a patient with measles hanging out in your waiting room. According to the American Academy of Pediatrics, measures to prevent the transmission of contagious infectious agents in ambulatory facilities begin at the time the visit is scheduled. When there is measles transmission in the community, consider using a standardized script when scheduling patients that includes questions about fever, rash, other symptoms typical for measles, and possible exposures. Some offices will have procedures in place that can be adapted to care for patients with suspected measles. When a patient presents for suspected chicken pox, do you advise them to come at the end of the day to minimize exposures? Enter through a side door? Perform a car visit?
Triage promptly. Mask patients with fever and rash, move to a private room, and close the door.
Once measles is suspected, only health care personnel who are immune to measles should enter the exam room. According to the Centers for Disease Control and Prevention, presumptive evidence of measles immunity in health care providers is written documentation of vaccination with two doses of live measles or MMR vaccine administered at least 28 days apart, laboratory evidence of immunity (that is, positive measles IgG), laboratory confirmation of disease, or birth before 1957.
Even though health care providers born before 1957 are presumed to have had the disease at some point and have traditionally been considered immune, the CDC suggests that health care facilities consider giving these individuals two doses of MMR vaccine unless they have prior laboratory confirmation of disease immunity. Do you know who in your office is immune or would you need to scramble if you had an exposure?
When measles is suspected, health care personnel should wear an N-95 if they have been fit tested and the appropriate mask is available. Practically, most ambulatory offices do not stock N-95 masks and the next best choice is a regular surgical mask.
Order the recommended tests to confirm the diagnosis, but do not wait for the results to confirm the diagnosis. The CDC recommends testing serum for IgM antibodies and sending a throat or nasopharyngeal swab to look for the virus by polymerase chain reaction testing. Measles virus also is shed in the urine so collecting a urine specimen for testing may increase the chances of finding the virus. Depending on where you practice, the tests may take 3 days or more to result. Contact your local health department as soon as you consider a measles diagnosis.
Discharge patients home or transferred to a higher level of care if this is necessary as quickly as possible. Fortunately, most patients with measles do not require hospitalization. Do not send patients to the hospital simply for the purpose of laboratory testing if this can be accomplished quickly in your office or for evaluation by other providers. This just creates the potential for more exposures. If a patient does require higher-level care, provider-to-provider communication about the suspected diagnosis and the need for airborne isolation should take place.
Keep the door closed. Once a patient with suspected measles is discharged from a regular exam room, the door should remain closed, and it should not be used for at least 1 hour. Remember that infectious virus can remain in the air for 1-2 hours after a patient leaves an area. The same is true for the waiting room.
Develop the exposure list. In general, patients and family members who were in the waiting room at the same time as the index patient and up to 1-2 hours after the index patient left are considered exposed. Measles is highly contagious and 9 out of 10 susceptible people who are exposed will develop disease. How many infants aged less than 1 year might be in your waiting room at any given time? How many immunocompromised patients or family members? Public health authorities can help determine who needs prophylaxis.
Don’t get anxious and start testing everyone for measles, especially patients who lack typical signs and symptoms or exposures. Ordering a test in a patient who has a low likelihood of measles is more likely to result in a false-positive test than a true-positive test. False-positive measles IgM tests can be seen with some viral infections, including parvovirus and Epstein-Barr. Some rheumatologic disorders also can contribute to false-positive tests.
Review your office procedure for vaccine counseling. The 10 month old with measles in the opening vignette should have been given an MMR vaccine before travel. The vaccine is recommended for infants aged 6-11 months who are traveling outside the United States, but it doesn’t count toward the vaccine series. Reimmunize young travelers at 12-15 months and again at 4-6 years. The CDC has developed a toolkit that contains resources for taking to parents about vaccines. It is available at https://www.cdc.gov/measles/toolkit/healthcare-providers.html.
It’s a typically busy Friday and the doctor is running 20 minutes behind schedule. He enters the next exam room and the sight of the patient makes him forget the apology he had prepared.
The 10 month old looks miserable. Red eyes. Snot dripping from his nose. A red rash that extends from his face and involves most of the chest, arms, and upper thighs.
“When did this start?” he asks the mother as he searches for a surgical mask in the cabinet next to the exam table.
“Two days after we returned from our vacation in France,” the worried young woman replies. “Do you think it could be measles?”
Between Jan. 1 and Aug. 8, 2019, 1,182 cases of measles had been confirmed in the United States. That’s more than three times the number of cases reported in all of 2018, and the highest number of cases reported in a single year in more than a quarter century. While 75% of the cases this year have been linked to outbreaks in New York, individuals from 30 states have been affected.
Given the widespread nature of the outbreak, With measles in particular, time is limited to deliver effective postexposure prophylaxis and prevent the spread of measles in the community, making it difficult to develop a plan on the fly.
Schedule strategically. You don’t want a patient with measles hanging out in your waiting room. According to the American Academy of Pediatrics, measures to prevent the transmission of contagious infectious agents in ambulatory facilities begin at the time the visit is scheduled. When there is measles transmission in the community, consider using a standardized script when scheduling patients that includes questions about fever, rash, other symptoms typical for measles, and possible exposures. Some offices will have procedures in place that can be adapted to care for patients with suspected measles. When a patient presents for suspected chicken pox, do you advise them to come at the end of the day to minimize exposures? Enter through a side door? Perform a car visit?
Triage promptly. Mask patients with fever and rash, move to a private room, and close the door.
Once measles is suspected, only health care personnel who are immune to measles should enter the exam room. According to the Centers for Disease Control and Prevention, presumptive evidence of measles immunity in health care providers is written documentation of vaccination with two doses of live measles or MMR vaccine administered at least 28 days apart, laboratory evidence of immunity (that is, positive measles IgG), laboratory confirmation of disease, or birth before 1957.
Even though health care providers born before 1957 are presumed to have had the disease at some point and have traditionally been considered immune, the CDC suggests that health care facilities consider giving these individuals two doses of MMR vaccine unless they have prior laboratory confirmation of disease immunity. Do you know who in your office is immune or would you need to scramble if you had an exposure?
When measles is suspected, health care personnel should wear an N-95 if they have been fit tested and the appropriate mask is available. Practically, most ambulatory offices do not stock N-95 masks and the next best choice is a regular surgical mask.
Order the recommended tests to confirm the diagnosis, but do not wait for the results to confirm the diagnosis. The CDC recommends testing serum for IgM antibodies and sending a throat or nasopharyngeal swab to look for the virus by polymerase chain reaction testing. Measles virus also is shed in the urine so collecting a urine specimen for testing may increase the chances of finding the virus. Depending on where you practice, the tests may take 3 days or more to result. Contact your local health department as soon as you consider a measles diagnosis.
Discharge patients home or transferred to a higher level of care if this is necessary as quickly as possible. Fortunately, most patients with measles do not require hospitalization. Do not send patients to the hospital simply for the purpose of laboratory testing if this can be accomplished quickly in your office or for evaluation by other providers. This just creates the potential for more exposures. If a patient does require higher-level care, provider-to-provider communication about the suspected diagnosis and the need for airborne isolation should take place.
Keep the door closed. Once a patient with suspected measles is discharged from a regular exam room, the door should remain closed, and it should not be used for at least 1 hour. Remember that infectious virus can remain in the air for 1-2 hours after a patient leaves an area. The same is true for the waiting room.
Develop the exposure list. In general, patients and family members who were in the waiting room at the same time as the index patient and up to 1-2 hours after the index patient left are considered exposed. Measles is highly contagious and 9 out of 10 susceptible people who are exposed will develop disease. How many infants aged less than 1 year might be in your waiting room at any given time? How many immunocompromised patients or family members? Public health authorities can help determine who needs prophylaxis.
Don’t get anxious and start testing everyone for measles, especially patients who lack typical signs and symptoms or exposures. Ordering a test in a patient who has a low likelihood of measles is more likely to result in a false-positive test than a true-positive test. False-positive measles IgM tests can be seen with some viral infections, including parvovirus and Epstein-Barr. Some rheumatologic disorders also can contribute to false-positive tests.
Review your office procedure for vaccine counseling. The 10 month old with measles in the opening vignette should have been given an MMR vaccine before travel. The vaccine is recommended for infants aged 6-11 months who are traveling outside the United States, but it doesn’t count toward the vaccine series. Reimmunize young travelers at 12-15 months and again at 4-6 years. The CDC has developed a toolkit that contains resources for taking to parents about vaccines. It is available at https://www.cdc.gov/measles/toolkit/healthcare-providers.html.
Nebraska issues SUNucate-based guidance for schools
Nebraska’s Department of Education recommended in a guidance that children be allowed to possess and use sunscreen products in school and at school-sponsored events, according to an Aug. 2 release from the American Society for Dermatologic Surgery.
The department’s guidance is based on model legislation developed by the SUNucate Coalition, which was created by the American Society for Dermatologic Surgery Association and “works to address barriers to sunscreen use in school and camps and promote sun-safe behavior.” The coalition was created in 2016 because of reports that some U.S. schools had banned sunscreen products as part of broader medication bans because of these products’ classification as an over-the-counter medication.
Twenty-three other states have moved to lift such bans; these states were joined by Arkansas, Connecticut, Illinois, Maine, Minnesota, Nevada, and now Nebraska in 2019 alone. The District of Columbia, Massachusetts, New Jersey, and Rhode Island are expected to follow suit.
Nebraska’s Department of Education recommended in a guidance that children be allowed to possess and use sunscreen products in school and at school-sponsored events, according to an Aug. 2 release from the American Society for Dermatologic Surgery.
The department’s guidance is based on model legislation developed by the SUNucate Coalition, which was created by the American Society for Dermatologic Surgery Association and “works to address barriers to sunscreen use in school and camps and promote sun-safe behavior.” The coalition was created in 2016 because of reports that some U.S. schools had banned sunscreen products as part of broader medication bans because of these products’ classification as an over-the-counter medication.
Twenty-three other states have moved to lift such bans; these states were joined by Arkansas, Connecticut, Illinois, Maine, Minnesota, Nevada, and now Nebraska in 2019 alone. The District of Columbia, Massachusetts, New Jersey, and Rhode Island are expected to follow suit.
Nebraska’s Department of Education recommended in a guidance that children be allowed to possess and use sunscreen products in school and at school-sponsored events, according to an Aug. 2 release from the American Society for Dermatologic Surgery.
The department’s guidance is based on model legislation developed by the SUNucate Coalition, which was created by the American Society for Dermatologic Surgery Association and “works to address barriers to sunscreen use in school and camps and promote sun-safe behavior.” The coalition was created in 2016 because of reports that some U.S. schools had banned sunscreen products as part of broader medication bans because of these products’ classification as an over-the-counter medication.
Twenty-three other states have moved to lift such bans; these states were joined by Arkansas, Connecticut, Illinois, Maine, Minnesota, Nevada, and now Nebraska in 2019 alone. The District of Columbia, Massachusetts, New Jersey, and Rhode Island are expected to follow suit.
‘Substantial burden’ of enterovirus meningitis in young infants
LJUBLJANA, SLOVENIA – A prospective international surveillance study has provided new insights into the surprisingly substantial clinical burden of viral meningitis caused by enteroviruses and human parechoviruses in young infants, Seilesh Kadambari, MBBS, PhD, said in his ESPID Young Investigator Award Lecture at the annual meeting of the European Society for Paediatric Infectious Diseases.
This comprehensive study captured all cases of laboratory-confirmed enterovirus (EV) and human parechovirus (HPeV) meningitis in infants less than 90 days old seen by pediatricians in the United Kingdom and Ireland during a 13-month period starting in July 2014, a time free of outbreaks. Dr. Kadambari, a pediatrician at the University of Oxford (England), was first author of the study. It was for this project, as well as his earlier studies shedding light on congenital viral infections, that he received the Young Investigator honor.
Among the key findings of the U.K./Ireland surveillance study: The incidence of EV/HPeV meningitis was more than twice that of bacterial meningitis in the same age group and more than fivefold higher than that of group B streptococcal meningitis, the No. 1 cause of bacterial meningitis in early infancy. Moreover, more than one-half of infants with EV/HPeV meningitis had low levels of inflammatory markers and no cerebrospinal fluid pleocytosis, which underscores the importance of routinely testing the cerebrospinal fluid for viral causes of meningitis in such patients using modern molecular tools such as multiplex polymerase chain reaction, according to Dr. Kadambari.
“Also, not a single one of the patients with EV/HPeV meningitis had a secondary bacterial infection – and that has important implications for management of our antibiotic stewardship programs,” he observed.
The study (Arch Dis Child. 2019 Jun;104(6):552-7) identified 668 cases of EV meningitis and 35 of HPeV meningitis, for an incidence of 0.79 and 0.04 per 1,000 live births, respectively. The most common clinical presentations were those generally seen in meningitis: fever, irritability, and reduced feeding. Circulatory shock was present in 43% of the infants with HPeV and 27% of the infants with EV infections.
Of infants with EV meningitis, 11% required admission to an intensive care unit, as did 23% of those with HPeV meningitis. Two babies with EV meningitis died and four others had continued neurologic complications at 12 months of follow-up. In contrast, all infants with HPeV survived without long-term sequelae.
Reassuringly, none of the 189 infants who underwent formal hearing testing had sensorineural hearing loss.
The surveillance study data have played an influential role in evidence-based guidelines for EV diagnosis and characterization published by the European Society of Clinical Virology (J Clin Virol. 2018 Apr;101:11-7).
An earlier study led by Dr. Kadambari documented a hefty sevenfold increase in the rate of laboratory-confirmed viral meningo-encephalitis in England and Wales during 2004-2013 across all age groups (J Infect. 2014 Oct;69[4]:326-32).
He attributed this increase to improved diagnosis of viral forms of meningitis through greater use of polymerase chain reaction. The study, based upon National Health Service hospital records, showed that more than 90% of all cases of viral meningo-encephalitis in infants less than 90 days old were caused by EV, a finding that prompted the subsequent prospective U.K./Ireland surveillance study.
Dr. Kadambari closed by noting the past decade had seen a greatly improved ability to diagnose congenital viral infections, but those improvements are not good enough.
“In the decade ahead, we hope to improve the management of this poorly understood group of infections,” the pediatrician promised.
Planned efforts include a cost-effectiveness analysis of a cytomegalovirus vaccine, an ESPID-funded research project aimed at identifying which EV/HPeV strains are most responsible for outbreaks and isolated severe disease, and gaining insight into the host-immunity factors associated with a proclivity to develop EV/HPeV meningitis in early infancy.
Dr. Kadambari reported having no financial conflicts regarding his studies, which was funded largely by Public Health England and university grants.
SOURCE: Kadambari S et al. Arch Dis Child. 2019;104:552-7.
LJUBLJANA, SLOVENIA – A prospective international surveillance study has provided new insights into the surprisingly substantial clinical burden of viral meningitis caused by enteroviruses and human parechoviruses in young infants, Seilesh Kadambari, MBBS, PhD, said in his ESPID Young Investigator Award Lecture at the annual meeting of the European Society for Paediatric Infectious Diseases.
This comprehensive study captured all cases of laboratory-confirmed enterovirus (EV) and human parechovirus (HPeV) meningitis in infants less than 90 days old seen by pediatricians in the United Kingdom and Ireland during a 13-month period starting in July 2014, a time free of outbreaks. Dr. Kadambari, a pediatrician at the University of Oxford (England), was first author of the study. It was for this project, as well as his earlier studies shedding light on congenital viral infections, that he received the Young Investigator honor.
Among the key findings of the U.K./Ireland surveillance study: The incidence of EV/HPeV meningitis was more than twice that of bacterial meningitis in the same age group and more than fivefold higher than that of group B streptococcal meningitis, the No. 1 cause of bacterial meningitis in early infancy. Moreover, more than one-half of infants with EV/HPeV meningitis had low levels of inflammatory markers and no cerebrospinal fluid pleocytosis, which underscores the importance of routinely testing the cerebrospinal fluid for viral causes of meningitis in such patients using modern molecular tools such as multiplex polymerase chain reaction, according to Dr. Kadambari.
“Also, not a single one of the patients with EV/HPeV meningitis had a secondary bacterial infection – and that has important implications for management of our antibiotic stewardship programs,” he observed.
The study (Arch Dis Child. 2019 Jun;104(6):552-7) identified 668 cases of EV meningitis and 35 of HPeV meningitis, for an incidence of 0.79 and 0.04 per 1,000 live births, respectively. The most common clinical presentations were those generally seen in meningitis: fever, irritability, and reduced feeding. Circulatory shock was present in 43% of the infants with HPeV and 27% of the infants with EV infections.
Of infants with EV meningitis, 11% required admission to an intensive care unit, as did 23% of those with HPeV meningitis. Two babies with EV meningitis died and four others had continued neurologic complications at 12 months of follow-up. In contrast, all infants with HPeV survived without long-term sequelae.
Reassuringly, none of the 189 infants who underwent formal hearing testing had sensorineural hearing loss.
The surveillance study data have played an influential role in evidence-based guidelines for EV diagnosis and characterization published by the European Society of Clinical Virology (J Clin Virol. 2018 Apr;101:11-7).
An earlier study led by Dr. Kadambari documented a hefty sevenfold increase in the rate of laboratory-confirmed viral meningo-encephalitis in England and Wales during 2004-2013 across all age groups (J Infect. 2014 Oct;69[4]:326-32).
He attributed this increase to improved diagnosis of viral forms of meningitis through greater use of polymerase chain reaction. The study, based upon National Health Service hospital records, showed that more than 90% of all cases of viral meningo-encephalitis in infants less than 90 days old were caused by EV, a finding that prompted the subsequent prospective U.K./Ireland surveillance study.
Dr. Kadambari closed by noting the past decade had seen a greatly improved ability to diagnose congenital viral infections, but those improvements are not good enough.
“In the decade ahead, we hope to improve the management of this poorly understood group of infections,” the pediatrician promised.
Planned efforts include a cost-effectiveness analysis of a cytomegalovirus vaccine, an ESPID-funded research project aimed at identifying which EV/HPeV strains are most responsible for outbreaks and isolated severe disease, and gaining insight into the host-immunity factors associated with a proclivity to develop EV/HPeV meningitis in early infancy.
Dr. Kadambari reported having no financial conflicts regarding his studies, which was funded largely by Public Health England and university grants.
SOURCE: Kadambari S et al. Arch Dis Child. 2019;104:552-7.
LJUBLJANA, SLOVENIA – A prospective international surveillance study has provided new insights into the surprisingly substantial clinical burden of viral meningitis caused by enteroviruses and human parechoviruses in young infants, Seilesh Kadambari, MBBS, PhD, said in his ESPID Young Investigator Award Lecture at the annual meeting of the European Society for Paediatric Infectious Diseases.
This comprehensive study captured all cases of laboratory-confirmed enterovirus (EV) and human parechovirus (HPeV) meningitis in infants less than 90 days old seen by pediatricians in the United Kingdom and Ireland during a 13-month period starting in July 2014, a time free of outbreaks. Dr. Kadambari, a pediatrician at the University of Oxford (England), was first author of the study. It was for this project, as well as his earlier studies shedding light on congenital viral infections, that he received the Young Investigator honor.
Among the key findings of the U.K./Ireland surveillance study: The incidence of EV/HPeV meningitis was more than twice that of bacterial meningitis in the same age group and more than fivefold higher than that of group B streptococcal meningitis, the No. 1 cause of bacterial meningitis in early infancy. Moreover, more than one-half of infants with EV/HPeV meningitis had low levels of inflammatory markers and no cerebrospinal fluid pleocytosis, which underscores the importance of routinely testing the cerebrospinal fluid for viral causes of meningitis in such patients using modern molecular tools such as multiplex polymerase chain reaction, according to Dr. Kadambari.
“Also, not a single one of the patients with EV/HPeV meningitis had a secondary bacterial infection – and that has important implications for management of our antibiotic stewardship programs,” he observed.
The study (Arch Dis Child. 2019 Jun;104(6):552-7) identified 668 cases of EV meningitis and 35 of HPeV meningitis, for an incidence of 0.79 and 0.04 per 1,000 live births, respectively. The most common clinical presentations were those generally seen in meningitis: fever, irritability, and reduced feeding. Circulatory shock was present in 43% of the infants with HPeV and 27% of the infants with EV infections.
Of infants with EV meningitis, 11% required admission to an intensive care unit, as did 23% of those with HPeV meningitis. Two babies with EV meningitis died and four others had continued neurologic complications at 12 months of follow-up. In contrast, all infants with HPeV survived without long-term sequelae.
Reassuringly, none of the 189 infants who underwent formal hearing testing had sensorineural hearing loss.
The surveillance study data have played an influential role in evidence-based guidelines for EV diagnosis and characterization published by the European Society of Clinical Virology (J Clin Virol. 2018 Apr;101:11-7).
An earlier study led by Dr. Kadambari documented a hefty sevenfold increase in the rate of laboratory-confirmed viral meningo-encephalitis in England and Wales during 2004-2013 across all age groups (J Infect. 2014 Oct;69[4]:326-32).
He attributed this increase to improved diagnosis of viral forms of meningitis through greater use of polymerase chain reaction. The study, based upon National Health Service hospital records, showed that more than 90% of all cases of viral meningo-encephalitis in infants less than 90 days old were caused by EV, a finding that prompted the subsequent prospective U.K./Ireland surveillance study.
Dr. Kadambari closed by noting the past decade had seen a greatly improved ability to diagnose congenital viral infections, but those improvements are not good enough.
“In the decade ahead, we hope to improve the management of this poorly understood group of infections,” the pediatrician promised.
Planned efforts include a cost-effectiveness analysis of a cytomegalovirus vaccine, an ESPID-funded research project aimed at identifying which EV/HPeV strains are most responsible for outbreaks and isolated severe disease, and gaining insight into the host-immunity factors associated with a proclivity to develop EV/HPeV meningitis in early infancy.
Dr. Kadambari reported having no financial conflicts regarding his studies, which was funded largely by Public Health England and university grants.
SOURCE: Kadambari S et al. Arch Dis Child. 2019;104:552-7.
REPORTING FROM ESPID 2019
A 2-month-old infant with a scalp rash that appeared after birth
With the perinatal history of prolonged labor and prolonged rupture of membranes, the diagnosis of halo scalp ring was made. This occurs secondary to prolonged pressure of the baby’s scalp with the mother’s pelvic bones, uterus, or cervical area, which causes decreased blood flow to the area, secondary ischemic damage, and in some cases scarring and hair loss.1
The degree of involvement is variable as some babies have mild alopecia and others have severe full-thickness necrosis and scarring. These lesions also can present with associated caput succedaneum and scalp molding, but these were not seen in our patient. Predisposing factors for halo scalp ring include caput succedaneum, prolonged or difficult labor, premature or prolonged rupture of membranes, vaginal delivery, vertex presentation, first delivery, as well as prematurity.2 On physical examination, a semicircular patch of alopecia with associated scarring, crusting, or erythema can be seen in some more severe cases.
The differential diagnosis includes aplasia cutis. In aplasia cutis, there is congenital loss of skin on the affected areas. The scalp usually is affected, but these lesions can occur in any other part of the body. Most patients with aplasia cutis have no other findings, but there are cases that can be associated with other cardiovascular, gastrointestinal, or central nervous system abnormalities. Neonatal lupus also can present with scarring lesions on the scalp, but they usually present a little after birth, mainly affecting the face. The mothers of this children usually have a diagnosis of connective tissue disease and may have positive antibodies to Sjögren’s syndrome antibody A, Sjögren’s syndrome antibody B, or antiribonucleoprotein antibody. Seborrheic dermatitis does not cause scarring alopecia. The lesions present as waxy scaly plaques on the scalp, erythematous waxy plaques behind the ears, face, and folds. Some patients can have hair loss secondary to the inflammation, but the hair grows back once the inflammation is controlled. Dissecting cellulitis is a type of scarring alopecia seen in pubescent and adult individuals. No cases of neonatal dissecting cellulitis have been described.
Halo scalp ring is not associated with any other systemic symptoms or syndromes. Extensive imaging and systemic work-up are not required unless the baby presents with other neurologic symptoms. The areas can be treated with petrolatum and observation as most lesions resolve.
In cases of extensive areas of scarring alopecia, referral to a plastic surgeon can be made to consider tissue expanders or scar revision prior to the child starting school if the lesions are causing psychological stressors.
The true prevalence of this condition is unknown. We believe halo ring alopecia is sometimes not diagnosed, and as lesions tend to resolve, most cases go unreported.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Email her at [email protected].
References
1. Arch Pediatr Adolesc Med. 2010;164(7):673.
2. Pediatr Dermatol. 2009 Nov-Dec;26(6):706-8.
3. Dermatol Online J. 2016 Nov 15;22(11).pii:13030/qt7rt592tz.
With the perinatal history of prolonged labor and prolonged rupture of membranes, the diagnosis of halo scalp ring was made. This occurs secondary to prolonged pressure of the baby’s scalp with the mother’s pelvic bones, uterus, or cervical area, which causes decreased blood flow to the area, secondary ischemic damage, and in some cases scarring and hair loss.1
The degree of involvement is variable as some babies have mild alopecia and others have severe full-thickness necrosis and scarring. These lesions also can present with associated caput succedaneum and scalp molding, but these were not seen in our patient. Predisposing factors for halo scalp ring include caput succedaneum, prolonged or difficult labor, premature or prolonged rupture of membranes, vaginal delivery, vertex presentation, first delivery, as well as prematurity.2 On physical examination, a semicircular patch of alopecia with associated scarring, crusting, or erythema can be seen in some more severe cases.
The differential diagnosis includes aplasia cutis. In aplasia cutis, there is congenital loss of skin on the affected areas. The scalp usually is affected, but these lesions can occur in any other part of the body. Most patients with aplasia cutis have no other findings, but there are cases that can be associated with other cardiovascular, gastrointestinal, or central nervous system abnormalities. Neonatal lupus also can present with scarring lesions on the scalp, but they usually present a little after birth, mainly affecting the face. The mothers of this children usually have a diagnosis of connective tissue disease and may have positive antibodies to Sjögren’s syndrome antibody A, Sjögren’s syndrome antibody B, or antiribonucleoprotein antibody. Seborrheic dermatitis does not cause scarring alopecia. The lesions present as waxy scaly plaques on the scalp, erythematous waxy plaques behind the ears, face, and folds. Some patients can have hair loss secondary to the inflammation, but the hair grows back once the inflammation is controlled. Dissecting cellulitis is a type of scarring alopecia seen in pubescent and adult individuals. No cases of neonatal dissecting cellulitis have been described.
Halo scalp ring is not associated with any other systemic symptoms or syndromes. Extensive imaging and systemic work-up are not required unless the baby presents with other neurologic symptoms. The areas can be treated with petrolatum and observation as most lesions resolve.
In cases of extensive areas of scarring alopecia, referral to a plastic surgeon can be made to consider tissue expanders or scar revision prior to the child starting school if the lesions are causing psychological stressors.
The true prevalence of this condition is unknown. We believe halo ring alopecia is sometimes not diagnosed, and as lesions tend to resolve, most cases go unreported.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Email her at [email protected].
References
1. Arch Pediatr Adolesc Med. 2010;164(7):673.
2. Pediatr Dermatol. 2009 Nov-Dec;26(6):706-8.
3. Dermatol Online J. 2016 Nov 15;22(11).pii:13030/qt7rt592tz.
With the perinatal history of prolonged labor and prolonged rupture of membranes, the diagnosis of halo scalp ring was made. This occurs secondary to prolonged pressure of the baby’s scalp with the mother’s pelvic bones, uterus, or cervical area, which causes decreased blood flow to the area, secondary ischemic damage, and in some cases scarring and hair loss.1
The degree of involvement is variable as some babies have mild alopecia and others have severe full-thickness necrosis and scarring. These lesions also can present with associated caput succedaneum and scalp molding, but these were not seen in our patient. Predisposing factors for halo scalp ring include caput succedaneum, prolonged or difficult labor, premature or prolonged rupture of membranes, vaginal delivery, vertex presentation, first delivery, as well as prematurity.2 On physical examination, a semicircular patch of alopecia with associated scarring, crusting, or erythema can be seen in some more severe cases.
The differential diagnosis includes aplasia cutis. In aplasia cutis, there is congenital loss of skin on the affected areas. The scalp usually is affected, but these lesions can occur in any other part of the body. Most patients with aplasia cutis have no other findings, but there are cases that can be associated with other cardiovascular, gastrointestinal, or central nervous system abnormalities. Neonatal lupus also can present with scarring lesions on the scalp, but they usually present a little after birth, mainly affecting the face. The mothers of this children usually have a diagnosis of connective tissue disease and may have positive antibodies to Sjögren’s syndrome antibody A, Sjögren’s syndrome antibody B, or antiribonucleoprotein antibody. Seborrheic dermatitis does not cause scarring alopecia. The lesions present as waxy scaly plaques on the scalp, erythematous waxy plaques behind the ears, face, and folds. Some patients can have hair loss secondary to the inflammation, but the hair grows back once the inflammation is controlled. Dissecting cellulitis is a type of scarring alopecia seen in pubescent and adult individuals. No cases of neonatal dissecting cellulitis have been described.
Halo scalp ring is not associated with any other systemic symptoms or syndromes. Extensive imaging and systemic work-up are not required unless the baby presents with other neurologic symptoms. The areas can be treated with petrolatum and observation as most lesions resolve.
In cases of extensive areas of scarring alopecia, referral to a plastic surgeon can be made to consider tissue expanders or scar revision prior to the child starting school if the lesions are causing psychological stressors.
The true prevalence of this condition is unknown. We believe halo ring alopecia is sometimes not diagnosed, and as lesions tend to resolve, most cases go unreported.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Email her at [email protected].
References
1. Arch Pediatr Adolesc Med. 2010;164(7):673.
2. Pediatr Dermatol. 2009 Nov-Dec;26(6):706-8.
3. Dermatol Online J. 2016 Nov 15;22(11).pii:13030/qt7rt592tz.
A 2-month-old male is referred to our pediatric dermatology clinic for evaluation of persistent seborrheic dermatitis. The mother reports that he presented with a rash on his scalp a few days after birth. She has been treating the crusted areas with clotrimazole and hydrocortisone and has noted improvement on the crusting, but now is worried that there is some scarring. The affected areas are not bleeding or tender. There are no other rashes elsewhere in the body.
He was born at 36 weeks from a 35-year-old gravida 1 para 0 woman with adequate prenatal care. The mother was diagnosed with preeclampsia and was induced. She had a prolonged labor and had premature rupture of membranes. The baby was delivered via cesarean section because of failure to progress and fetal distress; forceps, vacuum, and a scalp probe were not used during delivery. He was admitted to the neonatal unit for 5 days for sepsis work-up and respiratory distress. No intubation was needed.
Besides the preeclampsia, the mother denied any other medical conditions and was not taking any medications. He has met all developmental milestones for his age. He has no history of seizures.
On physical exam, there are semicircular patches of alopecia on the scalp. Some areas have pink, rubbery plaques with loss of hair follicles. On the frontal scalp, there are waxy plaques.
There is a blanchable violaceous patch on the occiput and there are some erythematous papules on the cheeks.
How to nearly eliminate CLABSIs in children’s hospitals
SEATTLE – Levine Children’s Hospital, in Charlotte, N.C., dropped its central line–associated bloodstream infection rate from 1.13 per 1,000 line days to 0.67 in just a few months, with a mix of common sense steps and public accountability.
Levine Children’s was at about the 50th percentile for CLABSIs, compared with other children’s hospitals, but dropped to the 10th percentile after the changes. There were 21 CLABSIs in 2017, but only 12 in 2018. The hospital went 6 straight months without a CLABSI after the changes were made. The efforts saved about $300,000 and 63 patient days.
“We really had great success,” said Kayla S. Koch, MD, a pediatric hospitalist at Levine Children’s, who presented the findings at Pediatric Hospital Medicine.
Hospital units had been working to reduce CLABSIs, but they were each doing their own thing. “Many of our units were already dabbling, so we just sort of brought them together. We standardized the process and got everyone on the same page,” said copresenter Ketan P. Nadkarni, MD, also a pediatric hospitalist at Levine Children’s.
It wasn’t hard to get buy-in. “I don’t think the units were aware that everyone was doing it differently,” and were on board once the problem was explained. Also, using the same approach throughout the hospital made it easier for nurses and physicians moving between units, he said.
Each morning, the nurse supervisor and patient nurse would partner up at the bedside to check that central venous lines were set up correctly. They examined the alcohol disinfectant caps to make sure they were clean; determined that children were getting chlorhexidine gluconate baths; checked the dressings for bleeding and soiling; noted in the electronic medical record why the patient had a central line; and discussed with hospitalists if it were still needed. Problems were addressed immediately.
These quality processes were all tracked on wall racks placed in plain sight on each unit, including the neonatal and pediatric ICUs. Each central line patient had a card that listed what needed to be done, with a green stripe on one side and a red stripe on the other. If everything was done right, the green side faced out; if even one thing was done wrong, the red side was displayed, for all to see. It brought accountability to the process, the presenters said at the meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
The wall rack also had the central line audit schedule, plus diagrams that showed every failed item, the reason for it, and the unit’s compliance rate. Anyone walking by could see at a glance how the unit was doing that day and overall.
The number of dressing options was reduced from 10 to 2, a SorbaView SHIELD and a Tegaderm-like dressing, which made it easier to standardize the efforts. A protocol also was put in place to reinforce oozing dressings, instead of automatically changing them. “We were doing too many changes,” Dr. Koch said.
Compliance with the bundle was almost 90%. Staff “really got into it, and it was great to see,” she said.
The “initial success was almost unexpected, and so dramatic.” The goal now is to sustain the improvements, and roll them out to radiology and other places were central lines are placed, Dr. Nadkarni said.
There was no external funding, and the investigators had no disclosures.
SEATTLE – Levine Children’s Hospital, in Charlotte, N.C., dropped its central line–associated bloodstream infection rate from 1.13 per 1,000 line days to 0.67 in just a few months, with a mix of common sense steps and public accountability.
Levine Children’s was at about the 50th percentile for CLABSIs, compared with other children’s hospitals, but dropped to the 10th percentile after the changes. There were 21 CLABSIs in 2017, but only 12 in 2018. The hospital went 6 straight months without a CLABSI after the changes were made. The efforts saved about $300,000 and 63 patient days.
“We really had great success,” said Kayla S. Koch, MD, a pediatric hospitalist at Levine Children’s, who presented the findings at Pediatric Hospital Medicine.
Hospital units had been working to reduce CLABSIs, but they were each doing their own thing. “Many of our units were already dabbling, so we just sort of brought them together. We standardized the process and got everyone on the same page,” said copresenter Ketan P. Nadkarni, MD, also a pediatric hospitalist at Levine Children’s.
It wasn’t hard to get buy-in. “I don’t think the units were aware that everyone was doing it differently,” and were on board once the problem was explained. Also, using the same approach throughout the hospital made it easier for nurses and physicians moving between units, he said.
Each morning, the nurse supervisor and patient nurse would partner up at the bedside to check that central venous lines were set up correctly. They examined the alcohol disinfectant caps to make sure they were clean; determined that children were getting chlorhexidine gluconate baths; checked the dressings for bleeding and soiling; noted in the electronic medical record why the patient had a central line; and discussed with hospitalists if it were still needed. Problems were addressed immediately.
These quality processes were all tracked on wall racks placed in plain sight on each unit, including the neonatal and pediatric ICUs. Each central line patient had a card that listed what needed to be done, with a green stripe on one side and a red stripe on the other. If everything was done right, the green side faced out; if even one thing was done wrong, the red side was displayed, for all to see. It brought accountability to the process, the presenters said at the meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
The wall rack also had the central line audit schedule, plus diagrams that showed every failed item, the reason for it, and the unit’s compliance rate. Anyone walking by could see at a glance how the unit was doing that day and overall.
The number of dressing options was reduced from 10 to 2, a SorbaView SHIELD and a Tegaderm-like dressing, which made it easier to standardize the efforts. A protocol also was put in place to reinforce oozing dressings, instead of automatically changing them. “We were doing too many changes,” Dr. Koch said.
Compliance with the bundle was almost 90%. Staff “really got into it, and it was great to see,” she said.
The “initial success was almost unexpected, and so dramatic.” The goal now is to sustain the improvements, and roll them out to radiology and other places were central lines are placed, Dr. Nadkarni said.
There was no external funding, and the investigators had no disclosures.
SEATTLE – Levine Children’s Hospital, in Charlotte, N.C., dropped its central line–associated bloodstream infection rate from 1.13 per 1,000 line days to 0.67 in just a few months, with a mix of common sense steps and public accountability.
Levine Children’s was at about the 50th percentile for CLABSIs, compared with other children’s hospitals, but dropped to the 10th percentile after the changes. There were 21 CLABSIs in 2017, but only 12 in 2018. The hospital went 6 straight months without a CLABSI after the changes were made. The efforts saved about $300,000 and 63 patient days.
“We really had great success,” said Kayla S. Koch, MD, a pediatric hospitalist at Levine Children’s, who presented the findings at Pediatric Hospital Medicine.
Hospital units had been working to reduce CLABSIs, but they were each doing their own thing. “Many of our units were already dabbling, so we just sort of brought them together. We standardized the process and got everyone on the same page,” said copresenter Ketan P. Nadkarni, MD, also a pediatric hospitalist at Levine Children’s.
It wasn’t hard to get buy-in. “I don’t think the units were aware that everyone was doing it differently,” and were on board once the problem was explained. Also, using the same approach throughout the hospital made it easier for nurses and physicians moving between units, he said.
Each morning, the nurse supervisor and patient nurse would partner up at the bedside to check that central venous lines were set up correctly. They examined the alcohol disinfectant caps to make sure they were clean; determined that children were getting chlorhexidine gluconate baths; checked the dressings for bleeding and soiling; noted in the electronic medical record why the patient had a central line; and discussed with hospitalists if it were still needed. Problems were addressed immediately.
These quality processes were all tracked on wall racks placed in plain sight on each unit, including the neonatal and pediatric ICUs. Each central line patient had a card that listed what needed to be done, with a green stripe on one side and a red stripe on the other. If everything was done right, the green side faced out; if even one thing was done wrong, the red side was displayed, for all to see. It brought accountability to the process, the presenters said at the meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.
The wall rack also had the central line audit schedule, plus diagrams that showed every failed item, the reason for it, and the unit’s compliance rate. Anyone walking by could see at a glance how the unit was doing that day and overall.
The number of dressing options was reduced from 10 to 2, a SorbaView SHIELD and a Tegaderm-like dressing, which made it easier to standardize the efforts. A protocol also was put in place to reinforce oozing dressings, instead of automatically changing them. “We were doing too many changes,” Dr. Koch said.
Compliance with the bundle was almost 90%. Staff “really got into it, and it was great to see,” she said.
The “initial success was almost unexpected, and so dramatic.” The goal now is to sustain the improvements, and roll them out to radiology and other places were central lines are placed, Dr. Nadkarni said.
There was no external funding, and the investigators had no disclosures.
REPORTING FROM PHM 2019