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Anidulafungin effectively treated invasive pediatric candidiasis in open-label trial
SAN DIEGO – The intravenous echinocandin anidulafungin effectively treated invasive candidiasis in a single-arm, multicenter, open-label trial of 47 children aged 2-17 years.
The overall global response rate of 72% resembled that from the prior adult registry study (76%), Emmanuel Roilides, MD, PhD, and his associates reported in a poster presented at an annual scientific meeting on infectious diseases.
At 6-week follow-up, two patients (4%) had relapsed, both with Candida parapsilosis, which was more resistant to treatment with anidulafungin (Eraxis) than other Candida species, the researchers reported. Treating the children with 3.0 mg/kg anidulafungin on day 1, followed by 1.5 mg/kg every 24 hours, yielded similar pharmacokinetics as the 200/100 mg regimen used in adults. The most common treatment-emergent adverse effects included diarrhea (23%), vomiting (23%), and fever (19%), which also reflected findings in adults, the investigators said. Five patients (10%) developed at least one severe treatment-emergent adverse event, including neutropenia, gastrointestinal hemorrhage, increased hepatic transaminases, hyponatremia, and myalgia. The study (NCT00761267) is ongoing and continues to recruit patients in 11 states in the United States and nine other countries, with final top-line results expected in 2019.
Although rates of invasive candidiasis appear to be decreasing in children overall, the population at risk is expanding, experts have noted. Relevant guidelines from the Infectious Disease Society of America and the European Society of Clinical Microbiology and Infectious Diseases list amphotericin B, echinocandins, and azoles as treatment options, but these recommendations are extrapolated mainly from adult studies, noted Dr. Roilides, who is a pediatric infectious disease specialist at Aristotle University School of Health Sciences and Hippokration General Hospital in Thessaloniki, Greece.
To better characterize the safety and efficacy of anidulafungin in children, the researchers enrolled patients up to 17 years of age who had signs and symptoms of invasive candidiasis and Candida cultured from a normally sterile site. Patients received intravenous anidulafungin (3 mg/kg on day 1, followed by 1.5 mg/kg every 24 hours) for at least 10 days, after which they could switch to oral fluconazole. Treatment continued for at least 14 days after blood cultures were negative and signs and symptoms resolved.
At interim data cutoff in October 2016, patients were exposed to anidulafungin for a median of 11.5 days (range, 1-28 days). Among 47 patients who received at least one dose of anidulafungin, about two-thirds were male, about 70% were white, and the average age was 8 years (standard deviation, 4.7 years). Rates of global success – a combination of clinical and microbiological response – were 82% in patients up to 5 years old and 67% in older children. Children whose baseline neutrophil count was at least 500 per mm3 had a 78% global response rate versus 50% among those with more severe neutropenia. C. parapsilosis had higher minimum inhibitory concentrations than other Candida species, and in vitro susceptibility rates of 85% for C. parapsilosis versus 100% for other species.
All patients experienced at least one treatment-emergent adverse effect. In addition to diarrhea, vomiting, and pyrexia, adverse events affecting more than 10% of patients included epistaxis (17%), headache (15%), and abdominal pain (13%). Half of patients switched to oral fluconazole. Four patients stopped treatment because of vomiting, generalized pruritus, or increased transaminases. A total of 15% of patients died, although no deaths were considered treatment related. The patient who stopped treatment because of pruritus later died of septic shock secondary to invasive candidiasis, despite having started treatment with fluconazole and micafungin, the investigators reported at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
Nearly all patients had bloodstream infections, and catheters also cultured positive in more than two-thirds of cases, the researchers said. Many patients had multiple risk factors for infection such as central venous catheters, broad-spectrum antibiotic therapy, total parenteral nutrition, and chemotherapy. Cultures were most often positive for Candida albicans (38%), followed by C. parapsilosis (26%) and C. tropicalis (13%).
Pfizer makes anidulafungin and sponsored the study. Dr. Roilides disclosed research grants and advisory relationships with Pfizer, Astellas, Gilead, and Merck.
SAN DIEGO – The intravenous echinocandin anidulafungin effectively treated invasive candidiasis in a single-arm, multicenter, open-label trial of 47 children aged 2-17 years.
The overall global response rate of 72% resembled that from the prior adult registry study (76%), Emmanuel Roilides, MD, PhD, and his associates reported in a poster presented at an annual scientific meeting on infectious diseases.
At 6-week follow-up, two patients (4%) had relapsed, both with Candida parapsilosis, which was more resistant to treatment with anidulafungin (Eraxis) than other Candida species, the researchers reported. Treating the children with 3.0 mg/kg anidulafungin on day 1, followed by 1.5 mg/kg every 24 hours, yielded similar pharmacokinetics as the 200/100 mg regimen used in adults. The most common treatment-emergent adverse effects included diarrhea (23%), vomiting (23%), and fever (19%), which also reflected findings in adults, the investigators said. Five patients (10%) developed at least one severe treatment-emergent adverse event, including neutropenia, gastrointestinal hemorrhage, increased hepatic transaminases, hyponatremia, and myalgia. The study (NCT00761267) is ongoing and continues to recruit patients in 11 states in the United States and nine other countries, with final top-line results expected in 2019.
Although rates of invasive candidiasis appear to be decreasing in children overall, the population at risk is expanding, experts have noted. Relevant guidelines from the Infectious Disease Society of America and the European Society of Clinical Microbiology and Infectious Diseases list amphotericin B, echinocandins, and azoles as treatment options, but these recommendations are extrapolated mainly from adult studies, noted Dr. Roilides, who is a pediatric infectious disease specialist at Aristotle University School of Health Sciences and Hippokration General Hospital in Thessaloniki, Greece.
To better characterize the safety and efficacy of anidulafungin in children, the researchers enrolled patients up to 17 years of age who had signs and symptoms of invasive candidiasis and Candida cultured from a normally sterile site. Patients received intravenous anidulafungin (3 mg/kg on day 1, followed by 1.5 mg/kg every 24 hours) for at least 10 days, after which they could switch to oral fluconazole. Treatment continued for at least 14 days after blood cultures were negative and signs and symptoms resolved.
At interim data cutoff in October 2016, patients were exposed to anidulafungin for a median of 11.5 days (range, 1-28 days). Among 47 patients who received at least one dose of anidulafungin, about two-thirds were male, about 70% were white, and the average age was 8 years (standard deviation, 4.7 years). Rates of global success – a combination of clinical and microbiological response – were 82% in patients up to 5 years old and 67% in older children. Children whose baseline neutrophil count was at least 500 per mm3 had a 78% global response rate versus 50% among those with more severe neutropenia. C. parapsilosis had higher minimum inhibitory concentrations than other Candida species, and in vitro susceptibility rates of 85% for C. parapsilosis versus 100% for other species.
All patients experienced at least one treatment-emergent adverse effect. In addition to diarrhea, vomiting, and pyrexia, adverse events affecting more than 10% of patients included epistaxis (17%), headache (15%), and abdominal pain (13%). Half of patients switched to oral fluconazole. Four patients stopped treatment because of vomiting, generalized pruritus, or increased transaminases. A total of 15% of patients died, although no deaths were considered treatment related. The patient who stopped treatment because of pruritus later died of septic shock secondary to invasive candidiasis, despite having started treatment with fluconazole and micafungin, the investigators reported at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
Nearly all patients had bloodstream infections, and catheters also cultured positive in more than two-thirds of cases, the researchers said. Many patients had multiple risk factors for infection such as central venous catheters, broad-spectrum antibiotic therapy, total parenteral nutrition, and chemotherapy. Cultures were most often positive for Candida albicans (38%), followed by C. parapsilosis (26%) and C. tropicalis (13%).
Pfizer makes anidulafungin and sponsored the study. Dr. Roilides disclosed research grants and advisory relationships with Pfizer, Astellas, Gilead, and Merck.
SAN DIEGO – The intravenous echinocandin anidulafungin effectively treated invasive candidiasis in a single-arm, multicenter, open-label trial of 47 children aged 2-17 years.
The overall global response rate of 72% resembled that from the prior adult registry study (76%), Emmanuel Roilides, MD, PhD, and his associates reported in a poster presented at an annual scientific meeting on infectious diseases.
At 6-week follow-up, two patients (4%) had relapsed, both with Candida parapsilosis, which was more resistant to treatment with anidulafungin (Eraxis) than other Candida species, the researchers reported. Treating the children with 3.0 mg/kg anidulafungin on day 1, followed by 1.5 mg/kg every 24 hours, yielded similar pharmacokinetics as the 200/100 mg regimen used in adults. The most common treatment-emergent adverse effects included diarrhea (23%), vomiting (23%), and fever (19%), which also reflected findings in adults, the investigators said. Five patients (10%) developed at least one severe treatment-emergent adverse event, including neutropenia, gastrointestinal hemorrhage, increased hepatic transaminases, hyponatremia, and myalgia. The study (NCT00761267) is ongoing and continues to recruit patients in 11 states in the United States and nine other countries, with final top-line results expected in 2019.
Although rates of invasive candidiasis appear to be decreasing in children overall, the population at risk is expanding, experts have noted. Relevant guidelines from the Infectious Disease Society of America and the European Society of Clinical Microbiology and Infectious Diseases list amphotericin B, echinocandins, and azoles as treatment options, but these recommendations are extrapolated mainly from adult studies, noted Dr. Roilides, who is a pediatric infectious disease specialist at Aristotle University School of Health Sciences and Hippokration General Hospital in Thessaloniki, Greece.
To better characterize the safety and efficacy of anidulafungin in children, the researchers enrolled patients up to 17 years of age who had signs and symptoms of invasive candidiasis and Candida cultured from a normally sterile site. Patients received intravenous anidulafungin (3 mg/kg on day 1, followed by 1.5 mg/kg every 24 hours) for at least 10 days, after which they could switch to oral fluconazole. Treatment continued for at least 14 days after blood cultures were negative and signs and symptoms resolved.
At interim data cutoff in October 2016, patients were exposed to anidulafungin for a median of 11.5 days (range, 1-28 days). Among 47 patients who received at least one dose of anidulafungin, about two-thirds were male, about 70% were white, and the average age was 8 years (standard deviation, 4.7 years). Rates of global success – a combination of clinical and microbiological response – were 82% in patients up to 5 years old and 67% in older children. Children whose baseline neutrophil count was at least 500 per mm3 had a 78% global response rate versus 50% among those with more severe neutropenia. C. parapsilosis had higher minimum inhibitory concentrations than other Candida species, and in vitro susceptibility rates of 85% for C. parapsilosis versus 100% for other species.
All patients experienced at least one treatment-emergent adverse effect. In addition to diarrhea, vomiting, and pyrexia, adverse events affecting more than 10% of patients included epistaxis (17%), headache (15%), and abdominal pain (13%). Half of patients switched to oral fluconazole. Four patients stopped treatment because of vomiting, generalized pruritus, or increased transaminases. A total of 15% of patients died, although no deaths were considered treatment related. The patient who stopped treatment because of pruritus later died of septic shock secondary to invasive candidiasis, despite having started treatment with fluconazole and micafungin, the investigators reported at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
Nearly all patients had bloodstream infections, and catheters also cultured positive in more than two-thirds of cases, the researchers said. Many patients had multiple risk factors for infection such as central venous catheters, broad-spectrum antibiotic therapy, total parenteral nutrition, and chemotherapy. Cultures were most often positive for Candida albicans (38%), followed by C. parapsilosis (26%) and C. tropicalis (13%).
Pfizer makes anidulafungin and sponsored the study. Dr. Roilides disclosed research grants and advisory relationships with Pfizer, Astellas, Gilead, and Merck.
AT IDWEEK 2017
Key clinical point: The intravenous echinocandin anidulafungin effectively treated invasive candidiasis in children, with a safety profile resembling what has been previously reported for adults.
Major finding: The overall global response rate was 72%. The most common treatment-emergent adverse effects included diarrhea (23%), vomiting (23%), and fever (19%). Five patients (10%) developed at least one severe treatment-emergent adverse event.
Data source: A multicenter, single-arm, open-label study of 47 patients aged 2-17 years.
Disclosures: Pfizer makes anidulafungin and sponsored the study. Dr. Roilides disclosed research grants and advisory relationships with Pfizer, Astellas, Gilead, and Merck.
Rectal temps in the nursery
It seems to me that the closer one could get to the center of the child’s body, the more likely you would get a true reading – and the less likely you would fall victim to operator error. However, a study reported on the Pediatric News website suggests that our intuition is wrong again (“Axillary thermometry is the best choice for newborns,” by M. Alexander Otto, Aug. 24, 2017). In the study of 205 newborns at the University of North Carolina at Chapel Hill Medical Center, multiple temperatures were recorded using three methods over a 15-minute period. Rectal temperatures were accurate but less reliable than axillary readings, while temporal artery measurements tended to “overestimate temperatures by an average of about a quarter of a degree.”
However, before we jump on the no-rectal-temps in the nursery bandwagon, let’s look at the rectal probe not just as a way to assess a newborn’s temperature, but as a tool for examining the baby’s rectum. For a variety of reasons, the newborn perineum often seems to escape the careful examination it deserves, particularly if the initial exam is performed with the parents watching.
Of course, parents are interested in their baby’s hair and eye color, and whether it has the requisite number of fingers and toes. They will wait anxiously until you have lifted your stethoscope off the baby’s chest and given them a nod and smile. However, doing a thorough exam of the infant’s genitalia may appear a bit invasive and improper to some parents. Whether it is because we sense some unspoken parental discomfort or because we are trying to save time, the nether regions of little girls are inadequately examined.
But back to rectal temperatures. It seems to me that it would be prudent to adopt a guideline that says that a newborn’s first temperature be taken rectally. Not because it is any more accurate than an axillary temperature – which this study suggests that it is not. But because the process of taking the temperature would make it more likely (I hesitate to say guarantee) that someone will be taking a careful look at the newborn’s rectum. That initial rectal temperature is not going to detect every genital anomaly, but it may help find some in a more timely fashion. If nothing else, it will get that meconium moving.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”
It seems to me that the closer one could get to the center of the child’s body, the more likely you would get a true reading – and the less likely you would fall victim to operator error. However, a study reported on the Pediatric News website suggests that our intuition is wrong again (“Axillary thermometry is the best choice for newborns,” by M. Alexander Otto, Aug. 24, 2017). In the study of 205 newborns at the University of North Carolina at Chapel Hill Medical Center, multiple temperatures were recorded using three methods over a 15-minute period. Rectal temperatures were accurate but less reliable than axillary readings, while temporal artery measurements tended to “overestimate temperatures by an average of about a quarter of a degree.”
However, before we jump on the no-rectal-temps in the nursery bandwagon, let’s look at the rectal probe not just as a way to assess a newborn’s temperature, but as a tool for examining the baby’s rectum. For a variety of reasons, the newborn perineum often seems to escape the careful examination it deserves, particularly if the initial exam is performed with the parents watching.
Of course, parents are interested in their baby’s hair and eye color, and whether it has the requisite number of fingers and toes. They will wait anxiously until you have lifted your stethoscope off the baby’s chest and given them a nod and smile. However, doing a thorough exam of the infant’s genitalia may appear a bit invasive and improper to some parents. Whether it is because we sense some unspoken parental discomfort or because we are trying to save time, the nether regions of little girls are inadequately examined.
But back to rectal temperatures. It seems to me that it would be prudent to adopt a guideline that says that a newborn’s first temperature be taken rectally. Not because it is any more accurate than an axillary temperature – which this study suggests that it is not. But because the process of taking the temperature would make it more likely (I hesitate to say guarantee) that someone will be taking a careful look at the newborn’s rectum. That initial rectal temperature is not going to detect every genital anomaly, but it may help find some in a more timely fashion. If nothing else, it will get that meconium moving.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”
It seems to me that the closer one could get to the center of the child’s body, the more likely you would get a true reading – and the less likely you would fall victim to operator error. However, a study reported on the Pediatric News website suggests that our intuition is wrong again (“Axillary thermometry is the best choice for newborns,” by M. Alexander Otto, Aug. 24, 2017). In the study of 205 newborns at the University of North Carolina at Chapel Hill Medical Center, multiple temperatures were recorded using three methods over a 15-minute period. Rectal temperatures were accurate but less reliable than axillary readings, while temporal artery measurements tended to “overestimate temperatures by an average of about a quarter of a degree.”
However, before we jump on the no-rectal-temps in the nursery bandwagon, let’s look at the rectal probe not just as a way to assess a newborn’s temperature, but as a tool for examining the baby’s rectum. For a variety of reasons, the newborn perineum often seems to escape the careful examination it deserves, particularly if the initial exam is performed with the parents watching.
Of course, parents are interested in their baby’s hair and eye color, and whether it has the requisite number of fingers and toes. They will wait anxiously until you have lifted your stethoscope off the baby’s chest and given them a nod and smile. However, doing a thorough exam of the infant’s genitalia may appear a bit invasive and improper to some parents. Whether it is because we sense some unspoken parental discomfort or because we are trying to save time, the nether regions of little girls are inadequately examined.
But back to rectal temperatures. It seems to me that it would be prudent to adopt a guideline that says that a newborn’s first temperature be taken rectally. Not because it is any more accurate than an axillary temperature – which this study suggests that it is not. But because the process of taking the temperature would make it more likely (I hesitate to say guarantee) that someone will be taking a careful look at the newborn’s rectum. That initial rectal temperature is not going to detect every genital anomaly, but it may help find some in a more timely fashion. If nothing else, it will get that meconium moving.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”
Maternal antepartum depression creates bevy of long-term risks in offspring
PARIS – Maternal depression during pregnancy is a common occurrence that can have far-reaching effects in the offspring, according to Tiina Taka-Eilola, MD, of the University of Oulu (Finland).
Indeed, maternal antepartum depression may best be thought of as an adverse environmental factor that exacerbates the impact of any underlying genetic vulnerability to severe mental disorder that may be present in the offspring, she said at the annual congress of the European College of Neuropsychopharmacology.
At midgestation, back in the mid-1960s, 13.9% of the mothers of the Northern Finland Birth Cohort acknowledged feeling “depressed” or “very depressed,” rates consistent with those reported in other studies using standardized depression assessment instruments. Their offspring, by age 43 years, were 1.6-fold more likely to have a history of a current or past nonpsychotic mood disorder and 2-fold more likely to have had a psychotic mood disorder than did the offspring of mothers free of antepartum depression.
These risks were greatly amplified if either parent experienced a hospital-treated severe mental disorder before, during, or up to 18 years after the pregnancy. Offspring who had both a mother who experienced antepartum depression and a parent with a severe, hospital-treated mental disorder were at 3.9-fold increased risk for being diagnosed with nonpsychotic depression by age 43 years in an analysis adjusted for sex, perinatal complications, and other potential confounders. They also were at 5.6-fold increased risk for psychotic depression and a whopping 7.8-fold greater risk of bipolar disorder than offspring with neither risk factor.
Moreover, in an earlier study, among men in the Northern Finland cohort who were assessed at age 33 years, investigators found that maternal depression during pregnancy was associated with an adjusted 1.4-fold increased likelihood of having a criminal record for a nonviolent offense, a 1.6-fold increased risk of violent crime, and a 1.7-fold increase in violent recidivism. In contrast, women whose mothers were depressed during pregnancy didn’t have a significantly higher rate of criminality, compared with those whose mothers weren’t depressed (J Affect Disord. 2003 May;74[3]:273-8).
In another earlier analysis, Dr. Taka-Eilola’s senior coinvestigators demonstrated that the risk of schizophrenia in the Northern Finland offspring was 2.6-fold greater if there was parental psychosis but no maternal antepartum depression than if neither was present, while the risk was 9.4-fold higher when both risk factors were present (Am J Psychiatry. 2010 Jan;167[1]:70-7).
Dr. Taka-Eilola, a primary care physician, said that postpartum depression garners news headlines and is far more extensively researched than is antepartum depression, but as the Finnish data show, antepartum depression is at least as common and deserves to be taken seriously. It’s important to screen for it and to treat it in an effort to prevent adverse effects in the offspring, as well as out of concern for the mother’s well-being, she emphasized. She believes this is now more likely to happen as a consequence of a recent World Psychiatric Association report calling for greater clinician attention to perinatal mental health.
Dr. Taka-Eilola reported having no financial conflicts of interest regarding the Northern Finland Birth Cohort Study, which is supported by the Academy of Finland, the Finnish Cultural Foundation Lapland Regional Fund, and grants from various nonprofit foundations.
PARIS – Maternal depression during pregnancy is a common occurrence that can have far-reaching effects in the offspring, according to Tiina Taka-Eilola, MD, of the University of Oulu (Finland).
Indeed, maternal antepartum depression may best be thought of as an adverse environmental factor that exacerbates the impact of any underlying genetic vulnerability to severe mental disorder that may be present in the offspring, she said at the annual congress of the European College of Neuropsychopharmacology.
At midgestation, back in the mid-1960s, 13.9% of the mothers of the Northern Finland Birth Cohort acknowledged feeling “depressed” or “very depressed,” rates consistent with those reported in other studies using standardized depression assessment instruments. Their offspring, by age 43 years, were 1.6-fold more likely to have a history of a current or past nonpsychotic mood disorder and 2-fold more likely to have had a psychotic mood disorder than did the offspring of mothers free of antepartum depression.
These risks were greatly amplified if either parent experienced a hospital-treated severe mental disorder before, during, or up to 18 years after the pregnancy. Offspring who had both a mother who experienced antepartum depression and a parent with a severe, hospital-treated mental disorder were at 3.9-fold increased risk for being diagnosed with nonpsychotic depression by age 43 years in an analysis adjusted for sex, perinatal complications, and other potential confounders. They also were at 5.6-fold increased risk for psychotic depression and a whopping 7.8-fold greater risk of bipolar disorder than offspring with neither risk factor.
Moreover, in an earlier study, among men in the Northern Finland cohort who were assessed at age 33 years, investigators found that maternal depression during pregnancy was associated with an adjusted 1.4-fold increased likelihood of having a criminal record for a nonviolent offense, a 1.6-fold increased risk of violent crime, and a 1.7-fold increase in violent recidivism. In contrast, women whose mothers were depressed during pregnancy didn’t have a significantly higher rate of criminality, compared with those whose mothers weren’t depressed (J Affect Disord. 2003 May;74[3]:273-8).
In another earlier analysis, Dr. Taka-Eilola’s senior coinvestigators demonstrated that the risk of schizophrenia in the Northern Finland offspring was 2.6-fold greater if there was parental psychosis but no maternal antepartum depression than if neither was present, while the risk was 9.4-fold higher when both risk factors were present (Am J Psychiatry. 2010 Jan;167[1]:70-7).
Dr. Taka-Eilola, a primary care physician, said that postpartum depression garners news headlines and is far more extensively researched than is antepartum depression, but as the Finnish data show, antepartum depression is at least as common and deserves to be taken seriously. It’s important to screen for it and to treat it in an effort to prevent adverse effects in the offspring, as well as out of concern for the mother’s well-being, she emphasized. She believes this is now more likely to happen as a consequence of a recent World Psychiatric Association report calling for greater clinician attention to perinatal mental health.
Dr. Taka-Eilola reported having no financial conflicts of interest regarding the Northern Finland Birth Cohort Study, which is supported by the Academy of Finland, the Finnish Cultural Foundation Lapland Regional Fund, and grants from various nonprofit foundations.
PARIS – Maternal depression during pregnancy is a common occurrence that can have far-reaching effects in the offspring, according to Tiina Taka-Eilola, MD, of the University of Oulu (Finland).
Indeed, maternal antepartum depression may best be thought of as an adverse environmental factor that exacerbates the impact of any underlying genetic vulnerability to severe mental disorder that may be present in the offspring, she said at the annual congress of the European College of Neuropsychopharmacology.
At midgestation, back in the mid-1960s, 13.9% of the mothers of the Northern Finland Birth Cohort acknowledged feeling “depressed” or “very depressed,” rates consistent with those reported in other studies using standardized depression assessment instruments. Their offspring, by age 43 years, were 1.6-fold more likely to have a history of a current or past nonpsychotic mood disorder and 2-fold more likely to have had a psychotic mood disorder than did the offspring of mothers free of antepartum depression.
These risks were greatly amplified if either parent experienced a hospital-treated severe mental disorder before, during, or up to 18 years after the pregnancy. Offspring who had both a mother who experienced antepartum depression and a parent with a severe, hospital-treated mental disorder were at 3.9-fold increased risk for being diagnosed with nonpsychotic depression by age 43 years in an analysis adjusted for sex, perinatal complications, and other potential confounders. They also were at 5.6-fold increased risk for psychotic depression and a whopping 7.8-fold greater risk of bipolar disorder than offspring with neither risk factor.
Moreover, in an earlier study, among men in the Northern Finland cohort who were assessed at age 33 years, investigators found that maternal depression during pregnancy was associated with an adjusted 1.4-fold increased likelihood of having a criminal record for a nonviolent offense, a 1.6-fold increased risk of violent crime, and a 1.7-fold increase in violent recidivism. In contrast, women whose mothers were depressed during pregnancy didn’t have a significantly higher rate of criminality, compared with those whose mothers weren’t depressed (J Affect Disord. 2003 May;74[3]:273-8).
In another earlier analysis, Dr. Taka-Eilola’s senior coinvestigators demonstrated that the risk of schizophrenia in the Northern Finland offspring was 2.6-fold greater if there was parental psychosis but no maternal antepartum depression than if neither was present, while the risk was 9.4-fold higher when both risk factors were present (Am J Psychiatry. 2010 Jan;167[1]:70-7).
Dr. Taka-Eilola, a primary care physician, said that postpartum depression garners news headlines and is far more extensively researched than is antepartum depression, but as the Finnish data show, antepartum depression is at least as common and deserves to be taken seriously. It’s important to screen for it and to treat it in an effort to prevent adverse effects in the offspring, as well as out of concern for the mother’s well-being, she emphasized. She believes this is now more likely to happen as a consequence of a recent World Psychiatric Association report calling for greater clinician attention to perinatal mental health.
Dr. Taka-Eilola reported having no financial conflicts of interest regarding the Northern Finland Birth Cohort Study, which is supported by the Academy of Finland, the Finnish Cultural Foundation Lapland Regional Fund, and grants from various nonprofit foundations.
AT THE ECNP CONGRESS
Key clinical point:
Major finding: By midlife, offspring of an mother who had antepartum depression and a parent with a severe, hospital-treated mental disorder were at an adjusted 5.6-fold increased risk for psychotic depression and 7.8-fold greater risk of bipolar disorder than the offspring with neither risk factor.
Data source: The Northern Finland Birth Cohort 1966 is an ongoing, observational, prospective, general population-based study of the 12,058 individuals born in the two northernmost provinces of Finland during 1966.
Disclosures: The presenter reported having no financial conflicts of interest regarding the study, which is supported by the Academy of Finland, the Finnish Cultural Foundation Lapland Regional Fund, and grants from various nonprofit foundations.
Five takeaways from Congress’ failure to extend funding for children’s coverage
Congress finally seems ready to take action on the Children’s Health Insurance Program after funding lapsed Sept. 30.
Before the deadline, lawmakers were busy grappling with the failed repeal of the Affordable Care Act.
CHIP covers 9 million children nationwide. But until Congress renews CHIP, states are cut off from additional federal funding that helps lower- and middle-income families.
CHIP, which has enjoyed broad bipartisan support, helps lower- and middle-income families that otherwise earn too much to be eligible for Medicaid. Besides children, it covers 370,000 pregnant women a year. Like Medicaid, CHIP is traditionally paid for with state and federal funds, but the federal government covers most of the cost.
Though current authorization for spending has expired, states can use some of their unspent federal CHIP money. Still, several states are expected to run out of money before the end of 2017, and most of the rest will run out by next summer. CHIP has been in this fix only one other time since it was established in 1997. In 2007, CHIP went weeks without funding authorization from Congress.
Here’s a quick look at what may lie ahead for the program.
1. Will children lose coverage because Congress missed the deadline?
They could eventually, but not immediately. A few states facing the most immediate threat – including California and Arizona – have enough funding to last only until the end of the year.
No states have yet announced plans to freeze enrollment or alert families about any potential end in coverage. But if Congress fails to renew funding quickly, some states may begin taking steps to unwind the program in the next few weeks.
2. What are states doing in reaction to Congress missing the deadline?
Most states are doing little except reaching into their unspent federal funds.
However, Minnesota was among those most imperiled because it had spent all its funds. State officials said Tuesday that the federal Centers for Medicare & Medicaid Services (CMS) was giving Minnesota $3.6 million from unspent national funds to cover CHIP this month.
Emily Piper, commissioner of the Minnesota Department of Human Services, reported in a newspaper commentary in September that her state’s funds would be exhausted by the end of that month.
Even without the last-minute infusion of funding from CMS, most of the children covered by CHIP would have continued to receive care under the state’s Medicaid program, but Minnesota would get fewer federal dollars for each child, according to Piper’s commentary. However, she added, those most at risk are the 1,700 pregnant women covered by CHIP, because they wouldn’t be eligible for Medicaid.
Utah has notified CMS that it plans to discontinue its CHIP program by the end of the year unless it receives more federal money. About 19,000 children are in the state’s CHIP program, state officials say. So far, though, the state said it is not moving to suspend service or enrollment or alert enrollees about any possible changes.
Nevada officials said if funding is not extended it might have to freeze enrollment on Nov. 1 and end coverage by Nov. 30.
California, which has 1.3 million children covered by CHIP, has the highest enrollment of any state running out of funding this year. But, so far, it’s continuing business as usual.
“We estimate that we have available CHIP funding at least through December 2017,” said Tony Cava, spokesman for California Department of Health Services. “Our CHIP program is open for enrollment and continues to operate normally.”
Oregon said it has enough CHIP funding to last through October for its program that covers 98,000 children.
3. When is Congress likely to act?
The Senate Finance and the House Energy and Commerce committees have scheduled votes Wednesday on legislation to extend CHIP funding. If both approve their individual bills, floor votes could come quickly, and then both houses would need to resolve any differences.
Senate Finance Committee Chairman Orrin Hatch (R-Utah) and the committee’s ranking Democrat, Sen. Ron Wyden of Oregon, announced an agreement in mid-September to renew CHIP funding. Under the proposed deal, federal CHIP funding would drop by 23 percentage points starting in by 2020, returning to its pre-Affordable Care Act levels. The agreement would extend the life of the CHIP program through 2022.
Hatch and Wyden did not provide any details on how they would pay for the CHIP extension.
The House Energy and Commerce Committee posted its bill just before midnight Monday. It mirrors the Senate Finance plan by extending funding for CHIP for five years and gradually phasing down the 23-percentage-point funding increase provided under Affordable Care Act over the next two years.
4. If CHIP is so popular among Republicans and Democrats, why hasn’t Congress renewed the program yet?
The funding renewal was not a priority among Republican leaders, who have spent most of this year trying to replace the Affordable Care Act and dramatically overhaul the Medicaid program. Some in Congress also thought the Sept. 30 deadline was squishy since states could extend their existing funds beyond that.
5. Who benefits from CHIP?
While CHIP income eligibility levels vary by state, about 90 percent of children covered are in families earning 200 percent of poverty or less ($40,840 for a family of three). CHIP covers children up to age 19. States have the option to cover pregnant women, and 18 plus the District of Columbia do so.
The program is known by different names in different states such as Hoosier Healthwise in Indiana and PeachCare for Kids in Georgia.
For families that move out of Medicaid as their incomes rise, CHIP is an affordable option that ensures continued coverage for their children. Many states operate their CHIP programs as part of Medicaid.
KHN’s coverage of children’s health care issues is supported in part by a grant from The Heising-Simons Foundation.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
Congress finally seems ready to take action on the Children’s Health Insurance Program after funding lapsed Sept. 30.
Before the deadline, lawmakers were busy grappling with the failed repeal of the Affordable Care Act.
CHIP covers 9 million children nationwide. But until Congress renews CHIP, states are cut off from additional federal funding that helps lower- and middle-income families.
CHIP, which has enjoyed broad bipartisan support, helps lower- and middle-income families that otherwise earn too much to be eligible for Medicaid. Besides children, it covers 370,000 pregnant women a year. Like Medicaid, CHIP is traditionally paid for with state and federal funds, but the federal government covers most of the cost.
Though current authorization for spending has expired, states can use some of their unspent federal CHIP money. Still, several states are expected to run out of money before the end of 2017, and most of the rest will run out by next summer. CHIP has been in this fix only one other time since it was established in 1997. In 2007, CHIP went weeks without funding authorization from Congress.
Here’s a quick look at what may lie ahead for the program.
1. Will children lose coverage because Congress missed the deadline?
They could eventually, but not immediately. A few states facing the most immediate threat – including California and Arizona – have enough funding to last only until the end of the year.
No states have yet announced plans to freeze enrollment or alert families about any potential end in coverage. But if Congress fails to renew funding quickly, some states may begin taking steps to unwind the program in the next few weeks.
2. What are states doing in reaction to Congress missing the deadline?
Most states are doing little except reaching into their unspent federal funds.
However, Minnesota was among those most imperiled because it had spent all its funds. State officials said Tuesday that the federal Centers for Medicare & Medicaid Services (CMS) was giving Minnesota $3.6 million from unspent national funds to cover CHIP this month.
Emily Piper, commissioner of the Minnesota Department of Human Services, reported in a newspaper commentary in September that her state’s funds would be exhausted by the end of that month.
Even without the last-minute infusion of funding from CMS, most of the children covered by CHIP would have continued to receive care under the state’s Medicaid program, but Minnesota would get fewer federal dollars for each child, according to Piper’s commentary. However, she added, those most at risk are the 1,700 pregnant women covered by CHIP, because they wouldn’t be eligible for Medicaid.
Utah has notified CMS that it plans to discontinue its CHIP program by the end of the year unless it receives more federal money. About 19,000 children are in the state’s CHIP program, state officials say. So far, though, the state said it is not moving to suspend service or enrollment or alert enrollees about any possible changes.
Nevada officials said if funding is not extended it might have to freeze enrollment on Nov. 1 and end coverage by Nov. 30.
California, which has 1.3 million children covered by CHIP, has the highest enrollment of any state running out of funding this year. But, so far, it’s continuing business as usual.
“We estimate that we have available CHIP funding at least through December 2017,” said Tony Cava, spokesman for California Department of Health Services. “Our CHIP program is open for enrollment and continues to operate normally.”
Oregon said it has enough CHIP funding to last through October for its program that covers 98,000 children.
3. When is Congress likely to act?
The Senate Finance and the House Energy and Commerce committees have scheduled votes Wednesday on legislation to extend CHIP funding. If both approve their individual bills, floor votes could come quickly, and then both houses would need to resolve any differences.
Senate Finance Committee Chairman Orrin Hatch (R-Utah) and the committee’s ranking Democrat, Sen. Ron Wyden of Oregon, announced an agreement in mid-September to renew CHIP funding. Under the proposed deal, federal CHIP funding would drop by 23 percentage points starting in by 2020, returning to its pre-Affordable Care Act levels. The agreement would extend the life of the CHIP program through 2022.
Hatch and Wyden did not provide any details on how they would pay for the CHIP extension.
The House Energy and Commerce Committee posted its bill just before midnight Monday. It mirrors the Senate Finance plan by extending funding for CHIP for five years and gradually phasing down the 23-percentage-point funding increase provided under Affordable Care Act over the next two years.
4. If CHIP is so popular among Republicans and Democrats, why hasn’t Congress renewed the program yet?
The funding renewal was not a priority among Republican leaders, who have spent most of this year trying to replace the Affordable Care Act and dramatically overhaul the Medicaid program. Some in Congress also thought the Sept. 30 deadline was squishy since states could extend their existing funds beyond that.
5. Who benefits from CHIP?
While CHIP income eligibility levels vary by state, about 90 percent of children covered are in families earning 200 percent of poverty or less ($40,840 for a family of three). CHIP covers children up to age 19. States have the option to cover pregnant women, and 18 plus the District of Columbia do so.
The program is known by different names in different states such as Hoosier Healthwise in Indiana and PeachCare for Kids in Georgia.
For families that move out of Medicaid as their incomes rise, CHIP is an affordable option that ensures continued coverage for their children. Many states operate their CHIP programs as part of Medicaid.
KHN’s coverage of children’s health care issues is supported in part by a grant from The Heising-Simons Foundation.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
Congress finally seems ready to take action on the Children’s Health Insurance Program after funding lapsed Sept. 30.
Before the deadline, lawmakers were busy grappling with the failed repeal of the Affordable Care Act.
CHIP covers 9 million children nationwide. But until Congress renews CHIP, states are cut off from additional federal funding that helps lower- and middle-income families.
CHIP, which has enjoyed broad bipartisan support, helps lower- and middle-income families that otherwise earn too much to be eligible for Medicaid. Besides children, it covers 370,000 pregnant women a year. Like Medicaid, CHIP is traditionally paid for with state and federal funds, but the federal government covers most of the cost.
Though current authorization for spending has expired, states can use some of their unspent federal CHIP money. Still, several states are expected to run out of money before the end of 2017, and most of the rest will run out by next summer. CHIP has been in this fix only one other time since it was established in 1997. In 2007, CHIP went weeks without funding authorization from Congress.
Here’s a quick look at what may lie ahead for the program.
1. Will children lose coverage because Congress missed the deadline?
They could eventually, but not immediately. A few states facing the most immediate threat – including California and Arizona – have enough funding to last only until the end of the year.
No states have yet announced plans to freeze enrollment or alert families about any potential end in coverage. But if Congress fails to renew funding quickly, some states may begin taking steps to unwind the program in the next few weeks.
2. What are states doing in reaction to Congress missing the deadline?
Most states are doing little except reaching into their unspent federal funds.
However, Minnesota was among those most imperiled because it had spent all its funds. State officials said Tuesday that the federal Centers for Medicare & Medicaid Services (CMS) was giving Minnesota $3.6 million from unspent national funds to cover CHIP this month.
Emily Piper, commissioner of the Minnesota Department of Human Services, reported in a newspaper commentary in September that her state’s funds would be exhausted by the end of that month.
Even without the last-minute infusion of funding from CMS, most of the children covered by CHIP would have continued to receive care under the state’s Medicaid program, but Minnesota would get fewer federal dollars for each child, according to Piper’s commentary. However, she added, those most at risk are the 1,700 pregnant women covered by CHIP, because they wouldn’t be eligible for Medicaid.
Utah has notified CMS that it plans to discontinue its CHIP program by the end of the year unless it receives more federal money. About 19,000 children are in the state’s CHIP program, state officials say. So far, though, the state said it is not moving to suspend service or enrollment or alert enrollees about any possible changes.
Nevada officials said if funding is not extended it might have to freeze enrollment on Nov. 1 and end coverage by Nov. 30.
California, which has 1.3 million children covered by CHIP, has the highest enrollment of any state running out of funding this year. But, so far, it’s continuing business as usual.
“We estimate that we have available CHIP funding at least through December 2017,” said Tony Cava, spokesman for California Department of Health Services. “Our CHIP program is open for enrollment and continues to operate normally.”
Oregon said it has enough CHIP funding to last through October for its program that covers 98,000 children.
3. When is Congress likely to act?
The Senate Finance and the House Energy and Commerce committees have scheduled votes Wednesday on legislation to extend CHIP funding. If both approve their individual bills, floor votes could come quickly, and then both houses would need to resolve any differences.
Senate Finance Committee Chairman Orrin Hatch (R-Utah) and the committee’s ranking Democrat, Sen. Ron Wyden of Oregon, announced an agreement in mid-September to renew CHIP funding. Under the proposed deal, federal CHIP funding would drop by 23 percentage points starting in by 2020, returning to its pre-Affordable Care Act levels. The agreement would extend the life of the CHIP program through 2022.
Hatch and Wyden did not provide any details on how they would pay for the CHIP extension.
The House Energy and Commerce Committee posted its bill just before midnight Monday. It mirrors the Senate Finance plan by extending funding for CHIP for five years and gradually phasing down the 23-percentage-point funding increase provided under Affordable Care Act over the next two years.
4. If CHIP is so popular among Republicans and Democrats, why hasn’t Congress renewed the program yet?
The funding renewal was not a priority among Republican leaders, who have spent most of this year trying to replace the Affordable Care Act and dramatically overhaul the Medicaid program. Some in Congress also thought the Sept. 30 deadline was squishy since states could extend their existing funds beyond that.
5. Who benefits from CHIP?
While CHIP income eligibility levels vary by state, about 90 percent of children covered are in families earning 200 percent of poverty or less ($40,840 for a family of three). CHIP covers children up to age 19. States have the option to cover pregnant women, and 18 plus the District of Columbia do so.
The program is known by different names in different states such as Hoosier Healthwise in Indiana and PeachCare for Kids in Georgia.
For families that move out of Medicaid as their incomes rise, CHIP is an affordable option that ensures continued coverage for their children. Many states operate their CHIP programs as part of Medicaid.
KHN’s coverage of children’s health care issues is supported in part by a grant from The Heising-Simons Foundation.
Kaiser Health News is a national health policy news service that is part of the nonpartisan Henry J. Kaiser Family Foundation.
Thinking may be shifting about first-line AOM treatment
CHICAGO – Treating even uncomplicated acute otitis media (AOM) in 2017 may not be as simple as writing an amoxicillin prescription. Changes in pathogens may mean a shift in prescribing practices, Ellen Wald, MD, said at the annual meeting of the American Academy of Pediatrics.
Dr. Wald, speaking to an audience that filled the lecture hall and an overflow room, said that there has long been good reason to turn to amoxicillin for AOM. “The reason that pediatricians and others like to reserve the use of amoxicillin as first-line therapy for children with AOM is that it is generally effective, it’s safe, it’s narrow in spectrum, and it’s relatively inexpensive. Those are all very desirable characteristics.”
However, the high-dose amoxicillin strategy is predicated on S. pneumoniae being the most likely cause of bacterial AOM. Since the seven-valent pneumococcal conjugate vaccine (PCV7), and then its successor PCV13, became part of the standard series of childhood immunizations, said Dr. Wald, the microbiology of AOM has shifted.
In 1990, S. pneumoniae was estimated to cause 35%-45% of AOM cases, with Haemophilus influenzae responsible for 25%-30% of cases. Moraxella catarrhalis was thought to cause 12%-15% of cases, with Streptococcus pyogenes–related AOM falling into the single digits.
In 2017, the balance has shifted, with S. pneumoniae only responsible for about a quarter of cases of AOM, and H. influenzae causing about half. The prevalence of M. catarrhalis and S. pyogenes cases hasn’t changed. This, said Dr. Wald, should prompt a shift in thinking about antibiotic strategy for AOM.
“The real problem with amoxicillin is that it’s not active against beta-lactamase–producing H. influenzae and M. catarrhalis. So my recommendation would be, rather than using amoxicillin, to use amoxicillin potassium clavulanate.”
Dr. Wald said she can’t currently recommend using azithromycin to treat AOM. “Azithromycin and the other macrolides have almost no activity against H. influenzae,” she said. “So given the current situation with the high prevalence of H. influenzae, azithromycin really should be avoided in the management of AOM.”
For children with non–type 1 penicillin hypersensitivity or mild type 1 hypersensitivity, a second- or third-generation cephalosporin, such as cefuroxime, cefpodoxime, or cefdinir, can be considered, she said.
“For life-threatening type 1 hypersensitivity reactions, we like to choose a drug of an entirely different class. For that reason, levofloxacin might be something you’d consider,” in those cases, said Dr. Wald, making clear that this is not a Food and Drug Administration–approved indication. Levofloxacin does have the antimicrobial spectrum to cover AOM pathogens, she said.
When parenteral therapy is indicated, as when a child isn’t tolerating oral medications or when nonadherence is likely, a single dose of ceftriaxone IM or IV, dosed at 50 mg/kg, remains a good option. “It’s a suitable agent because all middle ear pathogens are susceptible to ceftriaxone,” said Dr. Wald.
When oral antibiotics are used, how long should they be given? Some experts, she said, recommend a 5-day course for older children who have had infrequent previous episodes of AOM. In this age group, the shorter course can still yield an excellent response, she said.
However, a 2016 study that tried a shortened course of amoxicillin/clavulanate for children 6-23 months of age found that clinical failure occurred in 34% of the patients who received 5 days of antibiotics, compared with 16% of those who got the full 10-day course. “The recommendation is pretty clear that, for children under 2 years of age, a 10-day course of therapy is best,” said Dr. Wald.
Dr. Wald reported that she had no conflicts of interest.
koakes@frontlinemedcom.com
On Twitter @karioakes
CHICAGO – Treating even uncomplicated acute otitis media (AOM) in 2017 may not be as simple as writing an amoxicillin prescription. Changes in pathogens may mean a shift in prescribing practices, Ellen Wald, MD, said at the annual meeting of the American Academy of Pediatrics.
Dr. Wald, speaking to an audience that filled the lecture hall and an overflow room, said that there has long been good reason to turn to amoxicillin for AOM. “The reason that pediatricians and others like to reserve the use of amoxicillin as first-line therapy for children with AOM is that it is generally effective, it’s safe, it’s narrow in spectrum, and it’s relatively inexpensive. Those are all very desirable characteristics.”
However, the high-dose amoxicillin strategy is predicated on S. pneumoniae being the most likely cause of bacterial AOM. Since the seven-valent pneumococcal conjugate vaccine (PCV7), and then its successor PCV13, became part of the standard series of childhood immunizations, said Dr. Wald, the microbiology of AOM has shifted.
In 1990, S. pneumoniae was estimated to cause 35%-45% of AOM cases, with Haemophilus influenzae responsible for 25%-30% of cases. Moraxella catarrhalis was thought to cause 12%-15% of cases, with Streptococcus pyogenes–related AOM falling into the single digits.
In 2017, the balance has shifted, with S. pneumoniae only responsible for about a quarter of cases of AOM, and H. influenzae causing about half. The prevalence of M. catarrhalis and S. pyogenes cases hasn’t changed. This, said Dr. Wald, should prompt a shift in thinking about antibiotic strategy for AOM.
“The real problem with amoxicillin is that it’s not active against beta-lactamase–producing H. influenzae and M. catarrhalis. So my recommendation would be, rather than using amoxicillin, to use amoxicillin potassium clavulanate.”
Dr. Wald said she can’t currently recommend using azithromycin to treat AOM. “Azithromycin and the other macrolides have almost no activity against H. influenzae,” she said. “So given the current situation with the high prevalence of H. influenzae, azithromycin really should be avoided in the management of AOM.”
For children with non–type 1 penicillin hypersensitivity or mild type 1 hypersensitivity, a second- or third-generation cephalosporin, such as cefuroxime, cefpodoxime, or cefdinir, can be considered, she said.
“For life-threatening type 1 hypersensitivity reactions, we like to choose a drug of an entirely different class. For that reason, levofloxacin might be something you’d consider,” in those cases, said Dr. Wald, making clear that this is not a Food and Drug Administration–approved indication. Levofloxacin does have the antimicrobial spectrum to cover AOM pathogens, she said.
When parenteral therapy is indicated, as when a child isn’t tolerating oral medications or when nonadherence is likely, a single dose of ceftriaxone IM or IV, dosed at 50 mg/kg, remains a good option. “It’s a suitable agent because all middle ear pathogens are susceptible to ceftriaxone,” said Dr. Wald.
When oral antibiotics are used, how long should they be given? Some experts, she said, recommend a 5-day course for older children who have had infrequent previous episodes of AOM. In this age group, the shorter course can still yield an excellent response, she said.
However, a 2016 study that tried a shortened course of amoxicillin/clavulanate for children 6-23 months of age found that clinical failure occurred in 34% of the patients who received 5 days of antibiotics, compared with 16% of those who got the full 10-day course. “The recommendation is pretty clear that, for children under 2 years of age, a 10-day course of therapy is best,” said Dr. Wald.
Dr. Wald reported that she had no conflicts of interest.
koakes@frontlinemedcom.com
On Twitter @karioakes
CHICAGO – Treating even uncomplicated acute otitis media (AOM) in 2017 may not be as simple as writing an amoxicillin prescription. Changes in pathogens may mean a shift in prescribing practices, Ellen Wald, MD, said at the annual meeting of the American Academy of Pediatrics.
Dr. Wald, speaking to an audience that filled the lecture hall and an overflow room, said that there has long been good reason to turn to amoxicillin for AOM. “The reason that pediatricians and others like to reserve the use of amoxicillin as first-line therapy for children with AOM is that it is generally effective, it’s safe, it’s narrow in spectrum, and it’s relatively inexpensive. Those are all very desirable characteristics.”
However, the high-dose amoxicillin strategy is predicated on S. pneumoniae being the most likely cause of bacterial AOM. Since the seven-valent pneumococcal conjugate vaccine (PCV7), and then its successor PCV13, became part of the standard series of childhood immunizations, said Dr. Wald, the microbiology of AOM has shifted.
In 1990, S. pneumoniae was estimated to cause 35%-45% of AOM cases, with Haemophilus influenzae responsible for 25%-30% of cases. Moraxella catarrhalis was thought to cause 12%-15% of cases, with Streptococcus pyogenes–related AOM falling into the single digits.
In 2017, the balance has shifted, with S. pneumoniae only responsible for about a quarter of cases of AOM, and H. influenzae causing about half. The prevalence of M. catarrhalis and S. pyogenes cases hasn’t changed. This, said Dr. Wald, should prompt a shift in thinking about antibiotic strategy for AOM.
“The real problem with amoxicillin is that it’s not active against beta-lactamase–producing H. influenzae and M. catarrhalis. So my recommendation would be, rather than using amoxicillin, to use amoxicillin potassium clavulanate.”
Dr. Wald said she can’t currently recommend using azithromycin to treat AOM. “Azithromycin and the other macrolides have almost no activity against H. influenzae,” she said. “So given the current situation with the high prevalence of H. influenzae, azithromycin really should be avoided in the management of AOM.”
For children with non–type 1 penicillin hypersensitivity or mild type 1 hypersensitivity, a second- or third-generation cephalosporin, such as cefuroxime, cefpodoxime, or cefdinir, can be considered, she said.
“For life-threatening type 1 hypersensitivity reactions, we like to choose a drug of an entirely different class. For that reason, levofloxacin might be something you’d consider,” in those cases, said Dr. Wald, making clear that this is not a Food and Drug Administration–approved indication. Levofloxacin does have the antimicrobial spectrum to cover AOM pathogens, she said.
When parenteral therapy is indicated, as when a child isn’t tolerating oral medications or when nonadherence is likely, a single dose of ceftriaxone IM or IV, dosed at 50 mg/kg, remains a good option. “It’s a suitable agent because all middle ear pathogens are susceptible to ceftriaxone,” said Dr. Wald.
When oral antibiotics are used, how long should they be given? Some experts, she said, recommend a 5-day course for older children who have had infrequent previous episodes of AOM. In this age group, the shorter course can still yield an excellent response, she said.
However, a 2016 study that tried a shortened course of amoxicillin/clavulanate for children 6-23 months of age found that clinical failure occurred in 34% of the patients who received 5 days of antibiotics, compared with 16% of those who got the full 10-day course. “The recommendation is pretty clear that, for children under 2 years of age, a 10-day course of therapy is best,” said Dr. Wald.
Dr. Wald reported that she had no conflicts of interest.
koakes@frontlinemedcom.com
On Twitter @karioakes
EXPERT ANALYSIS FROM AAP 2017
Current pneumococcal vaccines knock out many serotypes, but others take their place
The introduction of pneumococcal conjugate vaccines 7 (PCV7) and 13 (PCV13) has significantly reduced pneumococcal colonization of the serotypes targeted by the vaccines, but serotypes not covered by these vaccines have picked up the slack, according to an analysis of more than 6,000 young Massachusetts children tested at well child or acute care visits over 15 years.
In the past 15 years, use of pneumococcal vaccines in the United States has led to dramatic declines in invasive pneumococcal disease (IPD) in young children, reductions in pneumonia hospitalizations, and herd protection in older adults against disease that otherwise would be caused by the vaccinated serotypes, studies have found. But not all serotypes of Streptococcus pneumoniae are covered by the vaccines.
The data used in the Massachusetts study included results from nasopharyngeal swabs taken from 6,537 children younger than 7 years of age in various Massachusetts communities during six respiratory illness seasons during 2000-2001, 2003-2004, 2006-2007, 2008-2009, 2010-2011, and 2013-2014. The highest rate of pneumococcal colonization was in 2011 at 32%, and the lowest was in 2004 at 23%, Grace M. Lee, MD, MPH, of the Harvard Medical School and Harvard Pilgrim Health Care Institute, both in Boston, and her associates reported (Pediatrics. 2017;140[3]:e20170001).
In 2001, PCV7 serotypes were the most common, but after the rapid introduction of the vaccine, infection rates for those serotypes quickly declined, nearly disappearing by 2007. Serotype 19A became the most common serotype in 2004, but after the introduction of PCV13 in 2010, it and other serotypes targeted by PCV13 also began to decline. In 2014, the most common serotypes were 15B/C, 35B, 23B, 11A, and 23A.
Non-PCV13 serotypes accounted for about a third of observed Streptococcus pneumoniae colonizations in 2001, but by 2014 they accounted for nearly all colonizations. In addition, the overall rate of infection did not decrease over the study period. While a reduction was seen from 2011 to 2014, it remains to be seen whether this drop is transient.
“Replacement with nonincluded serotypes remains a risk with vaccines that do not cover the full range of serotype diversity. As new selective pressures are applied, such as the introduction of a vaccine into a community, the void may be filled by nontargeted serotypes,” as was observed after PCV7, Dr. Lee and her fellow researchers noted.
Nonsusceptibility to erythromycin was most common in 2014, with 35% of pneumococcal isolates displaying either moderate susceptibility or resistance. Nonsusceptibility to ceftriaxone (12%), clindamycin (9%), and penicillin (6%) was significantly less common, and no isolates were found to have vancomycin resistance.
“First-line penicillins continue to be the most frequently prescribed antibiotic across all age groups among young children in Massachusetts, which may result in the continued success of 19A associated with penicillin resistance,” the researchers said.
Risk factors associated with colonization by either PCV13 serotypes or non-PCV13 serotypes include younger age, more hours of child care exposure, and having a respiratory tract infection on the day of sampling. The presence of a smoker in the house and recent usage of antibiotics was associated with colonization by PCV13 serotypes but not by non-PCV13 serotypes.
“As newer pneumococcal vaccines are developed, there will continue to be a need for monitoring both the intended and unintended consequences of altering the nasopharyngeal niche through immunization,” Dr. Lee and her associates concluded.
This work was funded by a National Institute of Allergy and Infectious Diseases grant and the National Institutes of Health. Marc Lipsitch, PhD; William P. Hanage, PhD; Ken Kleinman; Stephen Pelton, MD; and Susan S. Huang, MD, MPH, reported various conflicts of interest. Dr. Lee and the remaining investigators indicated that they had no potential conflicts of interest.
“The hope that IPD and antibiotic resistance would disappear after widespread use of PCV vaccines has yet to be realized,” Douglas S. Swanson, MD, and Christopher J. Harrison, MD, wrote in an accompanying editorial (Pediatrics. 2017;140[5]:e20172034).
While some invasive pneumococcal diseases, such as occult bacteremia and meningitis, have been significantly reduced due to PCV7 and PCV13, “one concern is whether some replacement serotypes could have invasive disease potential. For example, post-PCV7, there was increased severity of IPD from non-PCV7 serogroup organisms among children in the Intermountain West of the United States,” the authors noted. Newly dominant strains, such as post-PCV13 serotype 35B, could cause increased IPD in vulnerable populations, becoming the equivalent of a post-PCV7 serotype 19A.
While addressing emerging serotypes in additional PCVs is possible, reformulating the vaccine and obtaining Food and Drug Administration approval would take time and resources, with no clear guarantee of ultimate success, making “this strategy seem like playing a game of whack-a-mole. To overcome the phenomenon of serotype replacement, vaccine strategies need to expand beyond serotype specificity by identifying antigens common to all Streptococcus pneumoniae, regardless of serotype,” Dr. Swanson and Dr. Harrison said.
“Shifts back to less penicillin resistance may soon preclude the need for high dose amoxicillin for acute otitis media, and the near absence of occult Streptococcus pneumoniae bacteremia may drastically reduce empirical ceftriaxone for fever without a focus. To assist providers in ongoing vigilance for the now less frequent IPD, algorithms based on new epidemiologic data are in development and should decrease the number of ‘sepsis work-ups’ performed,” they said.
On-time PCV13 vaccination would help address the risk factor of young age, and judicious antibiotic use could further reduce antibiotic resistance. Social engineering approaches, although difficult, also might help. These approaches include continued parent education to restrict secondhand smoke exposure and the risk of S. pneumoniae nasopharyngeal colonization, as well as having young children spend fewer hours in day care in order to reduce two other risk factors – pathogen exposure and frequency of viral upper respiratory tract infections.
Dr. Swanson and Dr. Harrison are with the division of infectious diseases at Children’s Mercy Kansas City, University of Missouri-Kansas City. Both reported conducting pneumococcal research supported by funding from Pfizer.
“The hope that IPD and antibiotic resistance would disappear after widespread use of PCV vaccines has yet to be realized,” Douglas S. Swanson, MD, and Christopher J. Harrison, MD, wrote in an accompanying editorial (Pediatrics. 2017;140[5]:e20172034).
While some invasive pneumococcal diseases, such as occult bacteremia and meningitis, have been significantly reduced due to PCV7 and PCV13, “one concern is whether some replacement serotypes could have invasive disease potential. For example, post-PCV7, there was increased severity of IPD from non-PCV7 serogroup organisms among children in the Intermountain West of the United States,” the authors noted. Newly dominant strains, such as post-PCV13 serotype 35B, could cause increased IPD in vulnerable populations, becoming the equivalent of a post-PCV7 serotype 19A.
While addressing emerging serotypes in additional PCVs is possible, reformulating the vaccine and obtaining Food and Drug Administration approval would take time and resources, with no clear guarantee of ultimate success, making “this strategy seem like playing a game of whack-a-mole. To overcome the phenomenon of serotype replacement, vaccine strategies need to expand beyond serotype specificity by identifying antigens common to all Streptococcus pneumoniae, regardless of serotype,” Dr. Swanson and Dr. Harrison said.
“Shifts back to less penicillin resistance may soon preclude the need for high dose amoxicillin for acute otitis media, and the near absence of occult Streptococcus pneumoniae bacteremia may drastically reduce empirical ceftriaxone for fever without a focus. To assist providers in ongoing vigilance for the now less frequent IPD, algorithms based on new epidemiologic data are in development and should decrease the number of ‘sepsis work-ups’ performed,” they said.
On-time PCV13 vaccination would help address the risk factor of young age, and judicious antibiotic use could further reduce antibiotic resistance. Social engineering approaches, although difficult, also might help. These approaches include continued parent education to restrict secondhand smoke exposure and the risk of S. pneumoniae nasopharyngeal colonization, as well as having young children spend fewer hours in day care in order to reduce two other risk factors – pathogen exposure and frequency of viral upper respiratory tract infections.
Dr. Swanson and Dr. Harrison are with the division of infectious diseases at Children’s Mercy Kansas City, University of Missouri-Kansas City. Both reported conducting pneumococcal research supported by funding from Pfizer.
“The hope that IPD and antibiotic resistance would disappear after widespread use of PCV vaccines has yet to be realized,” Douglas S. Swanson, MD, and Christopher J. Harrison, MD, wrote in an accompanying editorial (Pediatrics. 2017;140[5]:e20172034).
While some invasive pneumococcal diseases, such as occult bacteremia and meningitis, have been significantly reduced due to PCV7 and PCV13, “one concern is whether some replacement serotypes could have invasive disease potential. For example, post-PCV7, there was increased severity of IPD from non-PCV7 serogroup organisms among children in the Intermountain West of the United States,” the authors noted. Newly dominant strains, such as post-PCV13 serotype 35B, could cause increased IPD in vulnerable populations, becoming the equivalent of a post-PCV7 serotype 19A.
While addressing emerging serotypes in additional PCVs is possible, reformulating the vaccine and obtaining Food and Drug Administration approval would take time and resources, with no clear guarantee of ultimate success, making “this strategy seem like playing a game of whack-a-mole. To overcome the phenomenon of serotype replacement, vaccine strategies need to expand beyond serotype specificity by identifying antigens common to all Streptococcus pneumoniae, regardless of serotype,” Dr. Swanson and Dr. Harrison said.
“Shifts back to less penicillin resistance may soon preclude the need for high dose amoxicillin for acute otitis media, and the near absence of occult Streptococcus pneumoniae bacteremia may drastically reduce empirical ceftriaxone for fever without a focus. To assist providers in ongoing vigilance for the now less frequent IPD, algorithms based on new epidemiologic data are in development and should decrease the number of ‘sepsis work-ups’ performed,” they said.
On-time PCV13 vaccination would help address the risk factor of young age, and judicious antibiotic use could further reduce antibiotic resistance. Social engineering approaches, although difficult, also might help. These approaches include continued parent education to restrict secondhand smoke exposure and the risk of S. pneumoniae nasopharyngeal colonization, as well as having young children spend fewer hours in day care in order to reduce two other risk factors – pathogen exposure and frequency of viral upper respiratory tract infections.
Dr. Swanson and Dr. Harrison are with the division of infectious diseases at Children’s Mercy Kansas City, University of Missouri-Kansas City. Both reported conducting pneumococcal research supported by funding from Pfizer.
The introduction of pneumococcal conjugate vaccines 7 (PCV7) and 13 (PCV13) has significantly reduced pneumococcal colonization of the serotypes targeted by the vaccines, but serotypes not covered by these vaccines have picked up the slack, according to an analysis of more than 6,000 young Massachusetts children tested at well child or acute care visits over 15 years.
In the past 15 years, use of pneumococcal vaccines in the United States has led to dramatic declines in invasive pneumococcal disease (IPD) in young children, reductions in pneumonia hospitalizations, and herd protection in older adults against disease that otherwise would be caused by the vaccinated serotypes, studies have found. But not all serotypes of Streptococcus pneumoniae are covered by the vaccines.
The data used in the Massachusetts study included results from nasopharyngeal swabs taken from 6,537 children younger than 7 years of age in various Massachusetts communities during six respiratory illness seasons during 2000-2001, 2003-2004, 2006-2007, 2008-2009, 2010-2011, and 2013-2014. The highest rate of pneumococcal colonization was in 2011 at 32%, and the lowest was in 2004 at 23%, Grace M. Lee, MD, MPH, of the Harvard Medical School and Harvard Pilgrim Health Care Institute, both in Boston, and her associates reported (Pediatrics. 2017;140[3]:e20170001).
In 2001, PCV7 serotypes were the most common, but after the rapid introduction of the vaccine, infection rates for those serotypes quickly declined, nearly disappearing by 2007. Serotype 19A became the most common serotype in 2004, but after the introduction of PCV13 in 2010, it and other serotypes targeted by PCV13 also began to decline. In 2014, the most common serotypes were 15B/C, 35B, 23B, 11A, and 23A.
Non-PCV13 serotypes accounted for about a third of observed Streptococcus pneumoniae colonizations in 2001, but by 2014 they accounted for nearly all colonizations. In addition, the overall rate of infection did not decrease over the study period. While a reduction was seen from 2011 to 2014, it remains to be seen whether this drop is transient.
“Replacement with nonincluded serotypes remains a risk with vaccines that do not cover the full range of serotype diversity. As new selective pressures are applied, such as the introduction of a vaccine into a community, the void may be filled by nontargeted serotypes,” as was observed after PCV7, Dr. Lee and her fellow researchers noted.
Nonsusceptibility to erythromycin was most common in 2014, with 35% of pneumococcal isolates displaying either moderate susceptibility or resistance. Nonsusceptibility to ceftriaxone (12%), clindamycin (9%), and penicillin (6%) was significantly less common, and no isolates were found to have vancomycin resistance.
“First-line penicillins continue to be the most frequently prescribed antibiotic across all age groups among young children in Massachusetts, which may result in the continued success of 19A associated with penicillin resistance,” the researchers said.
Risk factors associated with colonization by either PCV13 serotypes or non-PCV13 serotypes include younger age, more hours of child care exposure, and having a respiratory tract infection on the day of sampling. The presence of a smoker in the house and recent usage of antibiotics was associated with colonization by PCV13 serotypes but not by non-PCV13 serotypes.
“As newer pneumococcal vaccines are developed, there will continue to be a need for monitoring both the intended and unintended consequences of altering the nasopharyngeal niche through immunization,” Dr. Lee and her associates concluded.
This work was funded by a National Institute of Allergy and Infectious Diseases grant and the National Institutes of Health. Marc Lipsitch, PhD; William P. Hanage, PhD; Ken Kleinman; Stephen Pelton, MD; and Susan S. Huang, MD, MPH, reported various conflicts of interest. Dr. Lee and the remaining investigators indicated that they had no potential conflicts of interest.
The introduction of pneumococcal conjugate vaccines 7 (PCV7) and 13 (PCV13) has significantly reduced pneumococcal colonization of the serotypes targeted by the vaccines, but serotypes not covered by these vaccines have picked up the slack, according to an analysis of more than 6,000 young Massachusetts children tested at well child or acute care visits over 15 years.
In the past 15 years, use of pneumococcal vaccines in the United States has led to dramatic declines in invasive pneumococcal disease (IPD) in young children, reductions in pneumonia hospitalizations, and herd protection in older adults against disease that otherwise would be caused by the vaccinated serotypes, studies have found. But not all serotypes of Streptococcus pneumoniae are covered by the vaccines.
The data used in the Massachusetts study included results from nasopharyngeal swabs taken from 6,537 children younger than 7 years of age in various Massachusetts communities during six respiratory illness seasons during 2000-2001, 2003-2004, 2006-2007, 2008-2009, 2010-2011, and 2013-2014. The highest rate of pneumococcal colonization was in 2011 at 32%, and the lowest was in 2004 at 23%, Grace M. Lee, MD, MPH, of the Harvard Medical School and Harvard Pilgrim Health Care Institute, both in Boston, and her associates reported (Pediatrics. 2017;140[3]:e20170001).
In 2001, PCV7 serotypes were the most common, but after the rapid introduction of the vaccine, infection rates for those serotypes quickly declined, nearly disappearing by 2007. Serotype 19A became the most common serotype in 2004, but after the introduction of PCV13 in 2010, it and other serotypes targeted by PCV13 also began to decline. In 2014, the most common serotypes were 15B/C, 35B, 23B, 11A, and 23A.
Non-PCV13 serotypes accounted for about a third of observed Streptococcus pneumoniae colonizations in 2001, but by 2014 they accounted for nearly all colonizations. In addition, the overall rate of infection did not decrease over the study period. While a reduction was seen from 2011 to 2014, it remains to be seen whether this drop is transient.
“Replacement with nonincluded serotypes remains a risk with vaccines that do not cover the full range of serotype diversity. As new selective pressures are applied, such as the introduction of a vaccine into a community, the void may be filled by nontargeted serotypes,” as was observed after PCV7, Dr. Lee and her fellow researchers noted.
Nonsusceptibility to erythromycin was most common in 2014, with 35% of pneumococcal isolates displaying either moderate susceptibility or resistance. Nonsusceptibility to ceftriaxone (12%), clindamycin (9%), and penicillin (6%) was significantly less common, and no isolates were found to have vancomycin resistance.
“First-line penicillins continue to be the most frequently prescribed antibiotic across all age groups among young children in Massachusetts, which may result in the continued success of 19A associated with penicillin resistance,” the researchers said.
Risk factors associated with colonization by either PCV13 serotypes or non-PCV13 serotypes include younger age, more hours of child care exposure, and having a respiratory tract infection on the day of sampling. The presence of a smoker in the house and recent usage of antibiotics was associated with colonization by PCV13 serotypes but not by non-PCV13 serotypes.
“As newer pneumococcal vaccines are developed, there will continue to be a need for monitoring both the intended and unintended consequences of altering the nasopharyngeal niche through immunization,” Dr. Lee and her associates concluded.
This work was funded by a National Institute of Allergy and Infectious Diseases grant and the National Institutes of Health. Marc Lipsitch, PhD; William P. Hanage, PhD; Ken Kleinman; Stephen Pelton, MD; and Susan S. Huang, MD, MPH, reported various conflicts of interest. Dr. Lee and the remaining investigators indicated that they had no potential conflicts of interest.
FROM PEDIATRICS
Key clinical point:
Major finding: Serotype 19A became the most dominant serotype in 2004 but was significantly reduced by 2014 and replaced largely by serotypes 15B/C and 35B.
Data source: An analysis of pneumococcal serotypes in 6,537 children younger than 7 years of age who had well-child or acute care visits during six surveillance periods from 2000 to 2014.
Disclosures: This work was funded by a National Institute of Allergy and Infectious Diseases grant and the National Institutes of Health. Marc Lipsitch, PhD; William P. Hanage, PhD; Ken Kleinman; Stephen I. Pelton, MD; and Susan S. Huang, MD, MPH, reported various conflicts of interest. Dr. Lee and the remaining investigators indicated that they had no potential conflicts of interest.
IDWeek 2017 opens in San Diego
facing infectious diseases clinicians and researchers in the 21st century.
Premeeting workshops and symposia occupy most of the first 2 days of the event, with highlights including a session on managing infections in opioid users and a “late breaker” symposium addressing the latest on the H7N9 outbreak in China, the current findings and recommendations regarding Candida auris, and the epidemiology of the recent Legionella outbreaks in the United States. Another late breaker session focuses on the recent spate of hepatitis A outbreaks, including one in conference host city San Diego, primarily among the homeless population.
IDWeek is the combined annual meeting of the Infectious Diseases Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), and the Pediatric Infectious Diseases Society (PIDS). The first IDWeek was held in 2012.
One intriguing interactive session – aptly-titled “Nightmare Bugs” – will investigate the problems posed by multidrug-resistant organisms and the need for new antimicrobials to defeat them.
There are many sessions and posters addressing evergreen clinical topics for ID clinicians, such as antimicrobial resistance, antibiotic stewardship, surgical site infections, bacteremia and sepsis, Clostridium difficile, hepatitis care, and HIV care. But the education committee at IDWeek always manages to touch on topics in the news. For instance, one late breaker session will feature a discussion of the nexus between the opioid crisis and infectious diseases, the outbreak of cholera in Yemen, and the epidemiology of the yellow fever outbreak in Brazil.
Featured speakers at the event include James M. Hughes, MD, professor of medicine at Emory University, Atlanta, who will discuss the importance of a One Health approach to emerging microbial threats, and Connie Celum, MD, MPH, professor of global health and medicine, University of Washington, Seattle, who intends to describe the progress in effective HIV prevention interventions and lessons learned in implementation. Neil O. Fishman, MD, of the University of Pennsylvania Perelman School of Medicine, is delivering the annual SHEA lecture at IDWeek, and will explain how ID physicians and epidemiologists can promote interventions to achieve high reliability in health care. Renowned ID researcher Janet Englund, MD, of Seattle Children’s Hospital, will discuss the potential future therapies to prevent or treat respiratory viral infections in high-risk pediatric patients.
The 2017 conference will close with a three-part plenary – “21st Century Cures” – featuring ID luminaries Christopher Karp, MD, of the Bill & Melinda Gates Foundation, James E. Crowe Jr., MD, of Vanderbilt University Medical Center in Nashville, Tenn., and David Thomas, MD, MPH, of Johns Hopkins University in Baltimore.
rpizzi@frontlinemedcom.com
On Twitter @richpizzi
facing infectious diseases clinicians and researchers in the 21st century.
Premeeting workshops and symposia occupy most of the first 2 days of the event, with highlights including a session on managing infections in opioid users and a “late breaker” symposium addressing the latest on the H7N9 outbreak in China, the current findings and recommendations regarding Candida auris, and the epidemiology of the recent Legionella outbreaks in the United States. Another late breaker session focuses on the recent spate of hepatitis A outbreaks, including one in conference host city San Diego, primarily among the homeless population.
IDWeek is the combined annual meeting of the Infectious Diseases Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), and the Pediatric Infectious Diseases Society (PIDS). The first IDWeek was held in 2012.
One intriguing interactive session – aptly-titled “Nightmare Bugs” – will investigate the problems posed by multidrug-resistant organisms and the need for new antimicrobials to defeat them.
There are many sessions and posters addressing evergreen clinical topics for ID clinicians, such as antimicrobial resistance, antibiotic stewardship, surgical site infections, bacteremia and sepsis, Clostridium difficile, hepatitis care, and HIV care. But the education committee at IDWeek always manages to touch on topics in the news. For instance, one late breaker session will feature a discussion of the nexus between the opioid crisis and infectious diseases, the outbreak of cholera in Yemen, and the epidemiology of the yellow fever outbreak in Brazil.
Featured speakers at the event include James M. Hughes, MD, professor of medicine at Emory University, Atlanta, who will discuss the importance of a One Health approach to emerging microbial threats, and Connie Celum, MD, MPH, professor of global health and medicine, University of Washington, Seattle, who intends to describe the progress in effective HIV prevention interventions and lessons learned in implementation. Neil O. Fishman, MD, of the University of Pennsylvania Perelman School of Medicine, is delivering the annual SHEA lecture at IDWeek, and will explain how ID physicians and epidemiologists can promote interventions to achieve high reliability in health care. Renowned ID researcher Janet Englund, MD, of Seattle Children’s Hospital, will discuss the potential future therapies to prevent or treat respiratory viral infections in high-risk pediatric patients.
The 2017 conference will close with a three-part plenary – “21st Century Cures” – featuring ID luminaries Christopher Karp, MD, of the Bill & Melinda Gates Foundation, James E. Crowe Jr., MD, of Vanderbilt University Medical Center in Nashville, Tenn., and David Thomas, MD, MPH, of Johns Hopkins University in Baltimore.
rpizzi@frontlinemedcom.com
On Twitter @richpizzi
facing infectious diseases clinicians and researchers in the 21st century.
Premeeting workshops and symposia occupy most of the first 2 days of the event, with highlights including a session on managing infections in opioid users and a “late breaker” symposium addressing the latest on the H7N9 outbreak in China, the current findings and recommendations regarding Candida auris, and the epidemiology of the recent Legionella outbreaks in the United States. Another late breaker session focuses on the recent spate of hepatitis A outbreaks, including one in conference host city San Diego, primarily among the homeless population.
IDWeek is the combined annual meeting of the Infectious Diseases Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), and the Pediatric Infectious Diseases Society (PIDS). The first IDWeek was held in 2012.
One intriguing interactive session – aptly-titled “Nightmare Bugs” – will investigate the problems posed by multidrug-resistant organisms and the need for new antimicrobials to defeat them.
There are many sessions and posters addressing evergreen clinical topics for ID clinicians, such as antimicrobial resistance, antibiotic stewardship, surgical site infections, bacteremia and sepsis, Clostridium difficile, hepatitis care, and HIV care. But the education committee at IDWeek always manages to touch on topics in the news. For instance, one late breaker session will feature a discussion of the nexus between the opioid crisis and infectious diseases, the outbreak of cholera in Yemen, and the epidemiology of the yellow fever outbreak in Brazil.
Featured speakers at the event include James M. Hughes, MD, professor of medicine at Emory University, Atlanta, who will discuss the importance of a One Health approach to emerging microbial threats, and Connie Celum, MD, MPH, professor of global health and medicine, University of Washington, Seattle, who intends to describe the progress in effective HIV prevention interventions and lessons learned in implementation. Neil O. Fishman, MD, of the University of Pennsylvania Perelman School of Medicine, is delivering the annual SHEA lecture at IDWeek, and will explain how ID physicians and epidemiologists can promote interventions to achieve high reliability in health care. Renowned ID researcher Janet Englund, MD, of Seattle Children’s Hospital, will discuss the potential future therapies to prevent or treat respiratory viral infections in high-risk pediatric patients.
The 2017 conference will close with a three-part plenary – “21st Century Cures” – featuring ID luminaries Christopher Karp, MD, of the Bill & Melinda Gates Foundation, James E. Crowe Jr., MD, of Vanderbilt University Medical Center in Nashville, Tenn., and David Thomas, MD, MPH, of Johns Hopkins University in Baltimore.
rpizzi@frontlinemedcom.com
On Twitter @richpizzi
Healthy youth sports participation excludes early specialization
CHICAGO – When a boy receives five college football scholarship offers and a girl commits to playing soccer for a university before either of them starts ninth grade, it’s time to take several steps back in youth sports.
, including the risk of potentially discouraging a lifetime of healthy athletic participation, according to Joel S. Brenner, MD, MPH, a sports medicine expert at the Children’s Hospital of The King’s Daughters and Eastern Virginia Medical School, both in Norfolk.
“This paradigm should be discouraged by society,” Dr. Brenner told attendees at the American Academy of Pediatrics annual meeting. “Sports specialization refers to focusing on one sport to the exclusion of all others, often playing that single sport year-round. Dr. Brenner authored the AAP’s 2016 clinical report on sports specialization and intensive training in young athletes.
Dr. Brenner emphasized the benefits of delaying sports specialization until after puberty, the risks of specializing sooner, and the importance of rest to prevent burnout and injuries.
This is not a new problem, he noted, showing the attendees two Time Magazine covers, from 1999 and 2017, that featured the concern of “Sports Crazed Kids.” But it is so far-reaching that it will requires more than just physicians to change.
“This is not just an athlete problem, a parent problem, a coach problem, or even a physician problem,” Dr. Brenner said. “It’s a societal problem, a youth sports culture problem, and one that all of us as stakeholders need to attack and try to change the culture.”
Youth sports offer a broad range of benefits, such as developing physical activity, and leadership skills, and promoting self-esteem, socialization, and teamwork, Dr. Brenner said.
“But one benefit that often gets forgotten by people, including the coaches, the parents, and the athletes, is that sports is supposed to be about having fun,” he said.
The old model of kids’ sports was loosely organized fun, with kids playing multiple sports throughout the year and less direct involvement from adults, such as street hockey games and pick-up basketball. But those bygone days, Dr. Brenner noted wistfully, have been replaced with a different paradigm today: Children specialize in a single sport very early, and parents and coaches are the driving forces behind their involvement.
Today’s culture of very early sports specialization and college recruitment increases pressure on parents and young athletes to play year-round on multiple teams to stay on the radar of scouts and colleges. And this specialization has expanded to younger and younger ages, with 7-year-olds participating in travel leagues and national rankings of children in their sport as early as sixth grade.
“We should not be ranking kids in middle school or even in early high school,” Dr. Brenner said to wide applause. “We should allow kids to develop in a low-pressure, healthy system before we do that.”
The effects of high pressure have potentially lifelong ramifications. By the time children are 13 years old, 70% have dropped out of organized sports, Dr. Brenner said, and injuries from overuse account for more than half of all sports-related injuries in youth.
Yet the alternative – early diversification and late specialization – can really benefit kids, he said. The early specialization paradigm of playing just one sport focuses on deliberate practice and performance from the start. By contrast, early diversification with multiple sports focuses on deliberate play, during which children develop foundational athletic skills. Children who play a variety of sports are more likely to participate for more years – and it meets youth’s more realistic, long-term needs for lifelong physical activity through “fun, variety, and play,” he said.
Dr. Brenner said that just 1% of high school athletes receive any athletic scholarships, and only 3%-11% of high school athletes compete at the college level. The numbers for high school athletes that go on to play at the professional level is, of course, even smaller: 0.03% to 0.5%, depending on the sport.
And the irony is that the goal of early specialization – producing such elite level athletes – is actually better accomplished through playing multiple sports, Dr. Brenner said. Most Division 1 National Collegiate Athletic Association (NCAA) athletes and 90% of National Football League (NFL) first-round picks played multiple sports in high school. So the benefits of waiting until late adolescence to specialize are twofold: a greater likelihood of athletic success, even at elite levels, and minimizing the risks of injury.
Overuse injuries pose serious risks
More than half of sports injuries are from overuse, and a number of factors contribute to those injuries, such as muscle imbalance, playing surfaces, and training errors, Dr. Brenner said. But the biggest contributors are early specialization, playing year-round sports, and playing on multiple teams.
“This is a problem we see daily,” Dr. Brenner said. “We can see the young dancer, who’s dancing 6-7 days a week, who develops back pain and continues to dance, and develops a stress fracture in her lumbar spine known spondylosis.
“Or we see the young soccer player who plays on multiple teams and develops heel pain, who starts limping with activities of daily living, continues to play soccer despite limping, and develops calcaneal apophysitis, known as Sever’s disease. Or the young baseball pitcher, who pitches for two teams, who develops arm pain and weakness, who has a stress fracture through the proximal humeral epiphysis, known as Little League shoulder.” 
Two broad pieces of guidance can help reduce the risk of injuries, particularly from overuse. First, young athletes should take off at least 1 month from a specific sport at least three times a year to give them adequate time for physical and psychological recovery. Second, ensuring young athletes take at least 1 or 2 days off of practice each week further reduces the likelihood of injury.
In addition to the physical problems these young athletes may develop, they also risk anxiety, depression, burnout, early retirement, and social isolation from peers who don’t play their sport, Dr. Brenner said. Family members also may experience greater stress, he added. And then there’s the risk of missing out on learning other sports they may excel in that offer a lifetime of enjoyment, such as tennis or swimming.
It is not clear where the threshold of involvement is for reducing overuse injury, burnout, and attrition, but Dr. Brenner provided some guidelines as a starting place. High school athletes should not train more 16 hours a week, and organized sports should not exceed free play time by a greater ratio than 2:1. Another guideline is not to exceed more hours per week in organized sports than a child’s age in years.
The primary focus of sports should be learning lifelong physical activity skills and having fun, Dr. Brenner said. Pediatricians should encourage patients to play in a wide variety of sports at least until puberty, thereby decreasing the chance of injuries, stress, and burnout, he said. That can include sports that are not necessarily an official part of school or club competition. Waiting until later to specialize may lead to a higher likelihood of athletic success.
Dr. Brenner said he had no relevant financial disclosures.
CHICAGO – When a boy receives five college football scholarship offers and a girl commits to playing soccer for a university before either of them starts ninth grade, it’s time to take several steps back in youth sports.
, including the risk of potentially discouraging a lifetime of healthy athletic participation, according to Joel S. Brenner, MD, MPH, a sports medicine expert at the Children’s Hospital of The King’s Daughters and Eastern Virginia Medical School, both in Norfolk.
“This paradigm should be discouraged by society,” Dr. Brenner told attendees at the American Academy of Pediatrics annual meeting. “Sports specialization refers to focusing on one sport to the exclusion of all others, often playing that single sport year-round. Dr. Brenner authored the AAP’s 2016 clinical report on sports specialization and intensive training in young athletes.
Dr. Brenner emphasized the benefits of delaying sports specialization until after puberty, the risks of specializing sooner, and the importance of rest to prevent burnout and injuries.
This is not a new problem, he noted, showing the attendees two Time Magazine covers, from 1999 and 2017, that featured the concern of “Sports Crazed Kids.” But it is so far-reaching that it will requires more than just physicians to change.
“This is not just an athlete problem, a parent problem, a coach problem, or even a physician problem,” Dr. Brenner said. “It’s a societal problem, a youth sports culture problem, and one that all of us as stakeholders need to attack and try to change the culture.”
Youth sports offer a broad range of benefits, such as developing physical activity, and leadership skills, and promoting self-esteem, socialization, and teamwork, Dr. Brenner said.
“But one benefit that often gets forgotten by people, including the coaches, the parents, and the athletes, is that sports is supposed to be about having fun,” he said.
The old model of kids’ sports was loosely organized fun, with kids playing multiple sports throughout the year and less direct involvement from adults, such as street hockey games and pick-up basketball. But those bygone days, Dr. Brenner noted wistfully, have been replaced with a different paradigm today: Children specialize in a single sport very early, and parents and coaches are the driving forces behind their involvement.
Today’s culture of very early sports specialization and college recruitment increases pressure on parents and young athletes to play year-round on multiple teams to stay on the radar of scouts and colleges. And this specialization has expanded to younger and younger ages, with 7-year-olds participating in travel leagues and national rankings of children in their sport as early as sixth grade.
“We should not be ranking kids in middle school or even in early high school,” Dr. Brenner said to wide applause. “We should allow kids to develop in a low-pressure, healthy system before we do that.”
The effects of high pressure have potentially lifelong ramifications. By the time children are 13 years old, 70% have dropped out of organized sports, Dr. Brenner said, and injuries from overuse account for more than half of all sports-related injuries in youth.
Yet the alternative – early diversification and late specialization – can really benefit kids, he said. The early specialization paradigm of playing just one sport focuses on deliberate practice and performance from the start. By contrast, early diversification with multiple sports focuses on deliberate play, during which children develop foundational athletic skills. Children who play a variety of sports are more likely to participate for more years – and it meets youth’s more realistic, long-term needs for lifelong physical activity through “fun, variety, and play,” he said.
Dr. Brenner said that just 1% of high school athletes receive any athletic scholarships, and only 3%-11% of high school athletes compete at the college level. The numbers for high school athletes that go on to play at the professional level is, of course, even smaller: 0.03% to 0.5%, depending on the sport.
And the irony is that the goal of early specialization – producing such elite level athletes – is actually better accomplished through playing multiple sports, Dr. Brenner said. Most Division 1 National Collegiate Athletic Association (NCAA) athletes and 90% of National Football League (NFL) first-round picks played multiple sports in high school. So the benefits of waiting until late adolescence to specialize are twofold: a greater likelihood of athletic success, even at elite levels, and minimizing the risks of injury.
Overuse injuries pose serious risks
More than half of sports injuries are from overuse, and a number of factors contribute to those injuries, such as muscle imbalance, playing surfaces, and training errors, Dr. Brenner said. But the biggest contributors are early specialization, playing year-round sports, and playing on multiple teams.
“This is a problem we see daily,” Dr. Brenner said. “We can see the young dancer, who’s dancing 6-7 days a week, who develops back pain and continues to dance, and develops a stress fracture in her lumbar spine known spondylosis.
“Or we see the young soccer player who plays on multiple teams and develops heel pain, who starts limping with activities of daily living, continues to play soccer despite limping, and develops calcaneal apophysitis, known as Sever’s disease. Or the young baseball pitcher, who pitches for two teams, who develops arm pain and weakness, who has a stress fracture through the proximal humeral epiphysis, known as Little League shoulder.”
Two broad pieces of guidance can help reduce the risk of injuries, particularly from overuse. First, young athletes should take off at least 1 month from a specific sport at least three times a year to give them adequate time for physical and psychological recovery. Second, ensuring young athletes take at least 1 or 2 days off of practice each week further reduces the likelihood of injury.
In addition to the physical problems these young athletes may develop, they also risk anxiety, depression, burnout, early retirement, and social isolation from peers who don’t play their sport, Dr. Brenner said. Family members also may experience greater stress, he added. And then there’s the risk of missing out on learning other sports they may excel in that offer a lifetime of enjoyment, such as tennis or swimming.
It is not clear where the threshold of involvement is for reducing overuse injury, burnout, and attrition, but Dr. Brenner provided some guidelines as a starting place. High school athletes should not train more 16 hours a week, and organized sports should not exceed free play time by a greater ratio than 2:1. Another guideline is not to exceed more hours per week in organized sports than a child’s age in years.
The primary focus of sports should be learning lifelong physical activity skills and having fun, Dr. Brenner said. Pediatricians should encourage patients to play in a wide variety of sports at least until puberty, thereby decreasing the chance of injuries, stress, and burnout, he said. That can include sports that are not necessarily an official part of school or club competition. Waiting until later to specialize may lead to a higher likelihood of athletic success.
Dr. Brenner said he had no relevant financial disclosures.
CHICAGO – When a boy receives five college football scholarship offers and a girl commits to playing soccer for a university before either of them starts ninth grade, it’s time to take several steps back in youth sports.
, including the risk of potentially discouraging a lifetime of healthy athletic participation, according to Joel S. Brenner, MD, MPH, a sports medicine expert at the Children’s Hospital of The King’s Daughters and Eastern Virginia Medical School, both in Norfolk.
“This paradigm should be discouraged by society,” Dr. Brenner told attendees at the American Academy of Pediatrics annual meeting. “Sports specialization refers to focusing on one sport to the exclusion of all others, often playing that single sport year-round. Dr. Brenner authored the AAP’s 2016 clinical report on sports specialization and intensive training in young athletes.
Dr. Brenner emphasized the benefits of delaying sports specialization until after puberty, the risks of specializing sooner, and the importance of rest to prevent burnout and injuries.
This is not a new problem, he noted, showing the attendees two Time Magazine covers, from 1999 and 2017, that featured the concern of “Sports Crazed Kids.” But it is so far-reaching that it will requires more than just physicians to change.
“This is not just an athlete problem, a parent problem, a coach problem, or even a physician problem,” Dr. Brenner said. “It’s a societal problem, a youth sports culture problem, and one that all of us as stakeholders need to attack and try to change the culture.”
Youth sports offer a broad range of benefits, such as developing physical activity, and leadership skills, and promoting self-esteem, socialization, and teamwork, Dr. Brenner said.
“But one benefit that often gets forgotten by people, including the coaches, the parents, and the athletes, is that sports is supposed to be about having fun,” he said.
The old model of kids’ sports was loosely organized fun, with kids playing multiple sports throughout the year and less direct involvement from adults, such as street hockey games and pick-up basketball. But those bygone days, Dr. Brenner noted wistfully, have been replaced with a different paradigm today: Children specialize in a single sport very early, and parents and coaches are the driving forces behind their involvement.
Today’s culture of very early sports specialization and college recruitment increases pressure on parents and young athletes to play year-round on multiple teams to stay on the radar of scouts and colleges. And this specialization has expanded to younger and younger ages, with 7-year-olds participating in travel leagues and national rankings of children in their sport as early as sixth grade.
“We should not be ranking kids in middle school or even in early high school,” Dr. Brenner said to wide applause. “We should allow kids to develop in a low-pressure, healthy system before we do that.”
The effects of high pressure have potentially lifelong ramifications. By the time children are 13 years old, 70% have dropped out of organized sports, Dr. Brenner said, and injuries from overuse account for more than half of all sports-related injuries in youth.
Yet the alternative – early diversification and late specialization – can really benefit kids, he said. The early specialization paradigm of playing just one sport focuses on deliberate practice and performance from the start. By contrast, early diversification with multiple sports focuses on deliberate play, during which children develop foundational athletic skills. Children who play a variety of sports are more likely to participate for more years – and it meets youth’s more realistic, long-term needs for lifelong physical activity through “fun, variety, and play,” he said.
Dr. Brenner said that just 1% of high school athletes receive any athletic scholarships, and only 3%-11% of high school athletes compete at the college level. The numbers for high school athletes that go on to play at the professional level is, of course, even smaller: 0.03% to 0.5%, depending on the sport.
And the irony is that the goal of early specialization – producing such elite level athletes – is actually better accomplished through playing multiple sports, Dr. Brenner said. Most Division 1 National Collegiate Athletic Association (NCAA) athletes and 90% of National Football League (NFL) first-round picks played multiple sports in high school. So the benefits of waiting until late adolescence to specialize are twofold: a greater likelihood of athletic success, even at elite levels, and minimizing the risks of injury.
Overuse injuries pose serious risks
More than half of sports injuries are from overuse, and a number of factors contribute to those injuries, such as muscle imbalance, playing surfaces, and training errors, Dr. Brenner said. But the biggest contributors are early specialization, playing year-round sports, and playing on multiple teams.
“This is a problem we see daily,” Dr. Brenner said. “We can see the young dancer, who’s dancing 6-7 days a week, who develops back pain and continues to dance, and develops a stress fracture in her lumbar spine known spondylosis.
“Or we see the young soccer player who plays on multiple teams and develops heel pain, who starts limping with activities of daily living, continues to play soccer despite limping, and develops calcaneal apophysitis, known as Sever’s disease. Or the young baseball pitcher, who pitches for two teams, who develops arm pain and weakness, who has a stress fracture through the proximal humeral epiphysis, known as Little League shoulder.”
Two broad pieces of guidance can help reduce the risk of injuries, particularly from overuse. First, young athletes should take off at least 1 month from a specific sport at least three times a year to give them adequate time for physical and psychological recovery. Second, ensuring young athletes take at least 1 or 2 days off of practice each week further reduces the likelihood of injury.
In addition to the physical problems these young athletes may develop, they also risk anxiety, depression, burnout, early retirement, and social isolation from peers who don’t play their sport, Dr. Brenner said. Family members also may experience greater stress, he added. And then there’s the risk of missing out on learning other sports they may excel in that offer a lifetime of enjoyment, such as tennis or swimming.
It is not clear where the threshold of involvement is for reducing overuse injury, burnout, and attrition, but Dr. Brenner provided some guidelines as a starting place. High school athletes should not train more 16 hours a week, and organized sports should not exceed free play time by a greater ratio than 2:1. Another guideline is not to exceed more hours per week in organized sports than a child’s age in years.
The primary focus of sports should be learning lifelong physical activity skills and having fun, Dr. Brenner said. Pediatricians should encourage patients to play in a wide variety of sports at least until puberty, thereby decreasing the chance of injuries, stress, and burnout, he said. That can include sports that are not necessarily an official part of school or club competition. Waiting until later to specialize may lead to a higher likelihood of athletic success.
Dr. Brenner said he had no relevant financial disclosures.
EXPERT ANALYSIS FROM AAP 2017
Methylphenidate shows enduring sleep benefits in pediatric ADHD
PARIS – Methylphenidate therapy for attention-deficit/hyperactivity disorder in medication-naive boys significantly improved their sleep quality, timing, and duration in a double-blind randomized trial, Michelle M. Solleveld, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
Moreover, these salutary effects on sleep persisted for at least 1 week after methylphenidate was stopped at the end of the 16-week study, added Dr. Solleveld of the University of Amsterdam.
Indeed, while parents embrace the improvement in behavioral symptoms of ADHD provided by methylphenidate, they often express concern about the possible adverse effects of stimulant medication on their child’s sleep. The new study findings are reassuring on that score.
Sleep difficulties are a major problem in patients with ADHD: They tend to fall asleep later and have more frequent awakenings during the night, which results in decreased total sleep time and sleep efficiency, Dr. Solleveld noted.
Prior studies of methylphenidate’s effects on sleep in pediatric ADHD have yielded mixed results. The negative studies were too brief to provide meaningful results, according to Dr. Solleveld, who said at least 8 weeks of treatment are required in order to evaluate the drug’s effect on sleep problems properly.
She presented a randomized, double-blind, 16-week, placebo-controlled clinical trial involving 50 medication-naive boys with ADHD who were 10-12 years old. Their sleep was assessed via actigraphy measurements taken over 5 consecutive nights, keeping a sleep diary, and answering questionnaires, including the Epworth Sleepiness Scale, at three time points: prior to randomization, 8 weeks into the trial, and finally 1 week after the study ended.
Sleep efficiency – the primary study outcome – showed a strong 5% improvement in the methylphenidate group but was unchanged from baseline in placebo-treated controls. The boys who received methylphenidate fell asleep earlier, had a shorter latency of sleep onset, and slept for longer, compared with their baseline measures or with the sleep results in controls.
The finding that the methylphenidate-induced improvements in sleep persisted for a week after drug clearance is consistent with brain imaging studies carried out by Dr. Solleveld and her coinvestigators. They believe that the effects of stimulant therapy may be age dependent. The investigators previously have shown that adults with ADHD who began treatment with stimulants before age 16 years – when brain development is still ongoing – had lower levels of basal gamma-aminobutyric acid (GABA) and higher GABA response to an oral methylphenidate than did those who began treatment with stimulants after age 23 years. This is thought to be attributable to prolonged reductions in dopamine turnover induced by methylphenidate in the developing brain (Neuroimage Clin. 2017 Jun 2;15:812-8).
The Dutch investigators also have reported that methylphenidate therapy in children with ADHD – but not in affected adults – increased the cerebral blood flow response within the thalamus to a dopamine challenge (JAMA Psychiatry. 2016 Sep 1;73[9]:955-62).
The clinical ramifications of these apparently long-lasting, drug-related alterations in GABA neurotransmission are the subject of ongoing research.
Dr. Solleveld reported having no financial conflicts of interest.
PARIS – Methylphenidate therapy for attention-deficit/hyperactivity disorder in medication-naive boys significantly improved their sleep quality, timing, and duration in a double-blind randomized trial, Michelle M. Solleveld, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
Moreover, these salutary effects on sleep persisted for at least 1 week after methylphenidate was stopped at the end of the 16-week study, added Dr. Solleveld of the University of Amsterdam.
Indeed, while parents embrace the improvement in behavioral symptoms of ADHD provided by methylphenidate, they often express concern about the possible adverse effects of stimulant medication on their child’s sleep. The new study findings are reassuring on that score.
Sleep difficulties are a major problem in patients with ADHD: They tend to fall asleep later and have more frequent awakenings during the night, which results in decreased total sleep time and sleep efficiency, Dr. Solleveld noted.
Prior studies of methylphenidate’s effects on sleep in pediatric ADHD have yielded mixed results. The negative studies were too brief to provide meaningful results, according to Dr. Solleveld, who said at least 8 weeks of treatment are required in order to evaluate the drug’s effect on sleep problems properly.
She presented a randomized, double-blind, 16-week, placebo-controlled clinical trial involving 50 medication-naive boys with ADHD who were 10-12 years old. Their sleep was assessed via actigraphy measurements taken over 5 consecutive nights, keeping a sleep diary, and answering questionnaires, including the Epworth Sleepiness Scale, at three time points: prior to randomization, 8 weeks into the trial, and finally 1 week after the study ended.
Sleep efficiency – the primary study outcome – showed a strong 5% improvement in the methylphenidate group but was unchanged from baseline in placebo-treated controls. The boys who received methylphenidate fell asleep earlier, had a shorter latency of sleep onset, and slept for longer, compared with their baseline measures or with the sleep results in controls.
The finding that the methylphenidate-induced improvements in sleep persisted for a week after drug clearance is consistent with brain imaging studies carried out by Dr. Solleveld and her coinvestigators. They believe that the effects of stimulant therapy may be age dependent. The investigators previously have shown that adults with ADHD who began treatment with stimulants before age 16 years – when brain development is still ongoing – had lower levels of basal gamma-aminobutyric acid (GABA) and higher GABA response to an oral methylphenidate than did those who began treatment with stimulants after age 23 years. This is thought to be attributable to prolonged reductions in dopamine turnover induced by methylphenidate in the developing brain (Neuroimage Clin. 2017 Jun 2;15:812-8).
The Dutch investigators also have reported that methylphenidate therapy in children with ADHD – but not in affected adults – increased the cerebral blood flow response within the thalamus to a dopamine challenge (JAMA Psychiatry. 2016 Sep 1;73[9]:955-62).
The clinical ramifications of these apparently long-lasting, drug-related alterations in GABA neurotransmission are the subject of ongoing research.
Dr. Solleveld reported having no financial conflicts of interest.
PARIS – Methylphenidate therapy for attention-deficit/hyperactivity disorder in medication-naive boys significantly improved their sleep quality, timing, and duration in a double-blind randomized trial, Michelle M. Solleveld, MD, reported at the annual congress of the European College of Neuropsychopharmacology.
Moreover, these salutary effects on sleep persisted for at least 1 week after methylphenidate was stopped at the end of the 16-week study, added Dr. Solleveld of the University of Amsterdam.
Indeed, while parents embrace the improvement in behavioral symptoms of ADHD provided by methylphenidate, they often express concern about the possible adverse effects of stimulant medication on their child’s sleep. The new study findings are reassuring on that score.
Sleep difficulties are a major problem in patients with ADHD: They tend to fall asleep later and have more frequent awakenings during the night, which results in decreased total sleep time and sleep efficiency, Dr. Solleveld noted.
Prior studies of methylphenidate’s effects on sleep in pediatric ADHD have yielded mixed results. The negative studies were too brief to provide meaningful results, according to Dr. Solleveld, who said at least 8 weeks of treatment are required in order to evaluate the drug’s effect on sleep problems properly.
She presented a randomized, double-blind, 16-week, placebo-controlled clinical trial involving 50 medication-naive boys with ADHD who were 10-12 years old. Their sleep was assessed via actigraphy measurements taken over 5 consecutive nights, keeping a sleep diary, and answering questionnaires, including the Epworth Sleepiness Scale, at three time points: prior to randomization, 8 weeks into the trial, and finally 1 week after the study ended.
Sleep efficiency – the primary study outcome – showed a strong 5% improvement in the methylphenidate group but was unchanged from baseline in placebo-treated controls. The boys who received methylphenidate fell asleep earlier, had a shorter latency of sleep onset, and slept for longer, compared with their baseline measures or with the sleep results in controls.
The finding that the methylphenidate-induced improvements in sleep persisted for a week after drug clearance is consistent with brain imaging studies carried out by Dr. Solleveld and her coinvestigators. They believe that the effects of stimulant therapy may be age dependent. The investigators previously have shown that adults with ADHD who began treatment with stimulants before age 16 years – when brain development is still ongoing – had lower levels of basal gamma-aminobutyric acid (GABA) and higher GABA response to an oral methylphenidate than did those who began treatment with stimulants after age 23 years. This is thought to be attributable to prolonged reductions in dopamine turnover induced by methylphenidate in the developing brain (Neuroimage Clin. 2017 Jun 2;15:812-8).
The Dutch investigators also have reported that methylphenidate therapy in children with ADHD – but not in affected adults – increased the cerebral blood flow response within the thalamus to a dopamine challenge (JAMA Psychiatry. 2016 Sep 1;73[9]:955-62).
The clinical ramifications of these apparently long-lasting, drug-related alterations in GABA neurotransmission are the subject of ongoing research.
Dr. Solleveld reported having no financial conflicts of interest.
AT THE ECNP CONGRESS
Key clinical point:
Major finding: Sleep efficiency in boys with ADHD improved significantly by 5% in response to methylphenidate therapy.
Data source: This randomized, double-blind, placebo-controlled clinical trial included 50 medication-naive boys aged 10-12 years with ADHD.
Disclosures: The study presenter reported having no financial conflicts of interest.
Concurrent Sturge-Weber Syndrome, Facial Infantile Hemangioma, and Cutis Marmorata Telangiectatica Congenita
Sturge-Weber syndrome (SWS) is a disease of dermatologic, neurologic, and ocular significance.1 The most distinctive manifestation is facial capillary malformation, commonly referred to as a port-wine stain or nevus flammeus. The dysregulated angiogenesis, caused by somatic mutations of the G protein subunit alpha Q gene, GNAQ, also affects the central nervous system.2 Seizures, intellectual disability, and glaucoma are common consequences.1 Not all port-wine stains are associated with SWS.3 Distribution in the ophthalmic dermatome is associated with increased risk for SWS, with 8% of patients with port-wine stains also having SWS.4 The disease is more serious when bilateral lesions are present.5 Diagnosis is clinical based on dermatologic, nervous system, and ophthalmologic findings.6 The disease is nonheritable because the mutation is found only in the somatic cell lines.2 The possibility of epigenetic influence on disease development has to be investigated. The treatment is aimed at managing complications, as there is no cure.7
Infantile hemangioma (IH) likewise represents a disruption in the process of vascular development but without the widespread consequences of SWS. The pathogenesis of hemangioma development has not been fully elucidated, with presence of GLUT1 (glucose transporter 1) protein implicated in lesions.4 Facial infantile hemangiomas have an incidence of approximately 5 in every 100 births, and the prevalence decreases with age. Most hemangiomas undergo growth followed by an involution process, with most lesions vanishing by 5 years of age.4 They typically are seen at 2 to 3 weeks of age, growing rapidly for the first 6 months, which is a contrast to the static nature of nevus flammeus. Infantile hemangiomas are regarded as sporadic, though autosomal-dominant inheritance patterns have been observed.4 Our patient demonstrated facial IH at birth, which is a rare and interesting finding suggesting that some epigenetic factors influenced this modification of the disease course in this patient.
Cutis marmorata telangiectatica congenita (CMTC) is a rare cutaneous vascular condition found in newborns. Its extraordinary infrequency is reflected in the fact that only 300 cases have been reported worldwide.8 At birth, CMTC manifests as a pinkish reticulated pattern all over the body mimicking cutis marmorata; however, unlike cutis marmorata, the lesions do not improve with warming.9 The lesions of CMTC gradually lighten as the patient ages.8 Limb asymmetry is the most common extravascular complication of CMTC and, similar to SWS, glaucoma also can occur.10 Cutis marmorata telangiectatica congenita has been known to occur simultaneously with SWS or IH, but the combination of all 3 conditions in our patient is unique. Due to the scarcity of cases, the pathophysiology and treatment is poorly understood, with appropriate monitoring for sequelae recommended.9
Case Report
The patient was born at 39 weeks’ gestation following an uncomplicated pregnancy and delivery. She weighed 2950 g, her length was 19 in, and her head circumference was 13.25 in, correlating to the 10th, 50th, and 25th percentiles, respectively. Her Apgar score was 8/9 at 1 and 5 minutes. Her parents were nonconsanguineous and in good health. The patient’s family lived in poverty, which led us to conjecture about the role that toxins played in the epigenetics of the patient and her family. It was the mother’s third pregnancy; both prior pregnancies resulted in healthy children. The patient was breastfed. No family history of heritable vascular disorders was reported.
On the first day of life during the newborn examination, dark red pigment changes were noticed under the nose and erythematous pigmentation over the whole body was observed (Figure). On examination, 2-toned reticular lesions identified as extensive nevus flammeus were found bilaterally over the distribution of the ophthalmic division of the trigeminal nerve. A separate erythematous plaque over the maxilla also was recognized. The pediatrician suspected SWS and facial IH. The patient was discharged after 3 days with a referral to pediatric dermatology, and appropriate follow-up with a pediatrician was scheduled. The patient returned for these appointments and the significance of SWS was explained to her parents. Consultation with pediatric dermatology at 2 weeks of age confirmed the diagnosis of SWS as well as facial IH.
Upon further follow-up with pediatric dermatology at 2 months of age, the patient received an additional diagnosis of CMTC. These exceedingly rare lesions were located over the back, trunk, arms, and legs. The patient’s parents were counseled about the management of these conditions and appropriate follow-up.
Comment
This case describes 3 different vascular malformations in the same patient. Cutis marmorata telangiectatica congenita is rare and yet is described in this patient along with 2 other notable endothelial abnormalities. The clinical interest of this case is heightened by the presence of CMTC.
The causative factor of SWS is a well-documented mutation of the GNAQ gene, but there is considerable variability in how it affects the patient. Unlike in SWS, no single factor can be attributed to the development of IH. This case shows that these 3 diseases are not mutually exclusive and can present with unusually severe features when they occur concomitantly. The embryologic basis of SWS traces its roots back to the first trimester during vascular development, wher
The severity of the SWS in our patient was highlighted by the extensive nevus flammeus. These lesions occurred over the face, trunk, arms, and legs. The port-wine stain with dermatomal distribution of the ophthalmic nerve was the most concerning feature regarding the development of neurologic complications in this patient. Although the developmental delays associated with SWS can be serious, early intervention is important and can improve long-term outcomes. The facial IH arising at birth was contrary to the typical presentation. All of these factors will be kept in mind as the patient progresses and patient-centered care is provided. Because this patient’s presentation differed from other patients with IH, we will be more vigilant in providing close follow-up and monitoring for other medical problems involving other organs (eg, the brain); for instance, we will monitor for seizures and developmental delay.
Conclusion
In our patient, a unique pattern of SWS, facial IH, and CMTC are described in a pediatric patient. Many disciplines are involved in the treatment. In the patient’s first days of life, extensive collaboration between pediatrics and dermatologists was pivotal, with ophthalmology, pathology, and radiology consultations at hand. This case highlights that several vascular malformations of different origins can occur in the same patient. Epigenetic along with genetic factors likely contributed to this fascinating presentation. The importance of parental education and maintaining appropriate follow-up for this patient is crucial for a favorable outcome.
- Sinawat S, Auvichayapat N, Auvichayapat P, et al. 12-year retrospective study of Sturge-weber syndrome and literature review. J Med Assoc Thail. 2014;97:742-750.
- Shirley MD, Tang H, Gallione CJ, et al. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013;368:1971-1979.
- Sudarsanam A, Ardern-Holmes SL. Sturge-Weber syndrome: from the past to the present [published online November 7, 2013]. Eur J Paediat Neurol. 2014;18:257-266.
- Paller AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. Philadelphia, PA: Elsevier Saunders; 2011.
- Sujansky E, Conradi S. Sturge-Weber syndrome: age of onset of seizures and glaucoma and the prognosis for affected children. J Child Neurol. 1995;10:49-58.
- Lo W, Marchuk DA, Ball KL, et al. Updates and future horizons on the understanding, diagnosis, and treatment of Sturge-Weber syndrome brain involvement. Dev Med Child Neurol. 2012;54:214-223.
- Comi AM. Update on Sturge-Weber syndrome: diagnosis, treatment, quantitative measures, and controversies. Lymphat Res Biol. 2007;5:257-264.
- Resende CI, Araujo C, Vieira AP, et al. Cutis marmorata telangiectatica congenital [published online October 17, 2013]. BMJ Case Rep. doi:10.1136/bcr-2013-200056.
- Levy R, Lam JM. Cutis marmorata telangiectatica congenita: a mimicker of a common disorder. CMAJ. 2011;183:E249-E251.
- Kienast AK, Hoeger PH. Cutis marmorata telangiectatica congenita: a prospective study of 27 cases and review of the literature with proposal of diagnostic criteria. Clin Exp Dermatol. 2009;34:319-323.
- Comi AM. Topical review: pathophysiology of Sturge-Weber syndrome. J Child Neurol. 2003;18:509-516.
Sturge-Weber syndrome (SWS) is a disease of dermatologic, neurologic, and ocular significance.1 The most distinctive manifestation is facial capillary malformation, commonly referred to as a port-wine stain or nevus flammeus. The dysregulated angiogenesis, caused by somatic mutations of the G protein subunit alpha Q gene, GNAQ, also affects the central nervous system.2 Seizures, intellectual disability, and glaucoma are common consequences.1 Not all port-wine stains are associated with SWS.3 Distribution in the ophthalmic dermatome is associated with increased risk for SWS, with 8% of patients with port-wine stains also having SWS.4 The disease is more serious when bilateral lesions are present.5 Diagnosis is clinical based on dermatologic, nervous system, and ophthalmologic findings.6 The disease is nonheritable because the mutation is found only in the somatic cell lines.2 The possibility of epigenetic influence on disease development has to be investigated. The treatment is aimed at managing complications, as there is no cure.7
Infantile hemangioma (IH) likewise represents a disruption in the process of vascular development but without the widespread consequences of SWS. The pathogenesis of hemangioma development has not been fully elucidated, with presence of GLUT1 (glucose transporter 1) protein implicated in lesions.4 Facial infantile hemangiomas have an incidence of approximately 5 in every 100 births, and the prevalence decreases with age. Most hemangiomas undergo growth followed by an involution process, with most lesions vanishing by 5 years of age.4 They typically are seen at 2 to 3 weeks of age, growing rapidly for the first 6 months, which is a contrast to the static nature of nevus flammeus. Infantile hemangiomas are regarded as sporadic, though autosomal-dominant inheritance patterns have been observed.4 Our patient demonstrated facial IH at birth, which is a rare and interesting finding suggesting that some epigenetic factors influenced this modification of the disease course in this patient.
Cutis marmorata telangiectatica congenita (CMTC) is a rare cutaneous vascular condition found in newborns. Its extraordinary infrequency is reflected in the fact that only 300 cases have been reported worldwide.8 At birth, CMTC manifests as a pinkish reticulated pattern all over the body mimicking cutis marmorata; however, unlike cutis marmorata, the lesions do not improve with warming.9 The lesions of CMTC gradually lighten as the patient ages.8 Limb asymmetry is the most common extravascular complication of CMTC and, similar to SWS, glaucoma also can occur.10 Cutis marmorata telangiectatica congenita has been known to occur simultaneously with SWS or IH, but the combination of all 3 conditions in our patient is unique. Due to the scarcity of cases, the pathophysiology and treatment is poorly understood, with appropriate monitoring for sequelae recommended.9
Case Report
The patient was born at 39 weeks’ gestation following an uncomplicated pregnancy and delivery. She weighed 2950 g, her length was 19 in, and her head circumference was 13.25 in, correlating to the 10th, 50th, and 25th percentiles, respectively. Her Apgar score was 8/9 at 1 and 5 minutes. Her parents were nonconsanguineous and in good health. The patient’s family lived in poverty, which led us to conjecture about the role that toxins played in the epigenetics of the patient and her family. It was the mother’s third pregnancy; both prior pregnancies resulted in healthy children. The patient was breastfed. No family history of heritable vascular disorders was reported.
On the first day of life during the newborn examination, dark red pigment changes were noticed under the nose and erythematous pigmentation over the whole body was observed (Figure). On examination, 2-toned reticular lesions identified as extensive nevus flammeus were found bilaterally over the distribution of the ophthalmic division of the trigeminal nerve. A separate erythematous plaque over the maxilla also was recognized. The pediatrician suspected SWS and facial IH. The patient was discharged after 3 days with a referral to pediatric dermatology, and appropriate follow-up with a pediatrician was scheduled. The patient returned for these appointments and the significance of SWS was explained to her parents. Consultation with pediatric dermatology at 2 weeks of age confirmed the diagnosis of SWS as well as facial IH.
Upon further follow-up with pediatric dermatology at 2 months of age, the patient received an additional diagnosis of CMTC. These exceedingly rare lesions were located over the back, trunk, arms, and legs. The patient’s parents were counseled about the management of these conditions and appropriate follow-up.
Comment
This case describes 3 different vascular malformations in the same patient. Cutis marmorata telangiectatica congenita is rare and yet is described in this patient along with 2 other notable endothelial abnormalities. The clinical interest of this case is heightened by the presence of CMTC.
The causative factor of SWS is a well-documented mutation of the GNAQ gene, but there is considerable variability in how it affects the patient. Unlike in SWS, no single factor can be attributed to the development of IH. This case shows that these 3 diseases are not mutually exclusive and can present with unusually severe features when they occur concomitantly. The embryologic basis of SWS traces its roots back to the first trimester during vascular development, wher
The severity of the SWS in our patient was highlighted by the extensive nevus flammeus. These lesions occurred over the face, trunk, arms, and legs. The port-wine stain with dermatomal distribution of the ophthalmic nerve was the most concerning feature regarding the development of neurologic complications in this patient. Although the developmental delays associated with SWS can be serious, early intervention is important and can improve long-term outcomes. The facial IH arising at birth was contrary to the typical presentation. All of these factors will be kept in mind as the patient progresses and patient-centered care is provided. Because this patient’s presentation differed from other patients with IH, we will be more vigilant in providing close follow-up and monitoring for other medical problems involving other organs (eg, the brain); for instance, we will monitor for seizures and developmental delay.
Conclusion
In our patient, a unique pattern of SWS, facial IH, and CMTC are described in a pediatric patient. Many disciplines are involved in the treatment. In the patient’s first days of life, extensive collaboration between pediatrics and dermatologists was pivotal, with ophthalmology, pathology, and radiology consultations at hand. This case highlights that several vascular malformations of different origins can occur in the same patient. Epigenetic along with genetic factors likely contributed to this fascinating presentation. The importance of parental education and maintaining appropriate follow-up for this patient is crucial for a favorable outcome.
Sturge-Weber syndrome (SWS) is a disease of dermatologic, neurologic, and ocular significance.1 The most distinctive manifestation is facial capillary malformation, commonly referred to as a port-wine stain or nevus flammeus. The dysregulated angiogenesis, caused by somatic mutations of the G protein subunit alpha Q gene, GNAQ, also affects the central nervous system.2 Seizures, intellectual disability, and glaucoma are common consequences.1 Not all port-wine stains are associated with SWS.3 Distribution in the ophthalmic dermatome is associated with increased risk for SWS, with 8% of patients with port-wine stains also having SWS.4 The disease is more serious when bilateral lesions are present.5 Diagnosis is clinical based on dermatologic, nervous system, and ophthalmologic findings.6 The disease is nonheritable because the mutation is found only in the somatic cell lines.2 The possibility of epigenetic influence on disease development has to be investigated. The treatment is aimed at managing complications, as there is no cure.7
Infantile hemangioma (IH) likewise represents a disruption in the process of vascular development but without the widespread consequences of SWS. The pathogenesis of hemangioma development has not been fully elucidated, with presence of GLUT1 (glucose transporter 1) protein implicated in lesions.4 Facial infantile hemangiomas have an incidence of approximately 5 in every 100 births, and the prevalence decreases with age. Most hemangiomas undergo growth followed by an involution process, with most lesions vanishing by 5 years of age.4 They typically are seen at 2 to 3 weeks of age, growing rapidly for the first 6 months, which is a contrast to the static nature of nevus flammeus. Infantile hemangiomas are regarded as sporadic, though autosomal-dominant inheritance patterns have been observed.4 Our patient demonstrated facial IH at birth, which is a rare and interesting finding suggesting that some epigenetic factors influenced this modification of the disease course in this patient.
Cutis marmorata telangiectatica congenita (CMTC) is a rare cutaneous vascular condition found in newborns. Its extraordinary infrequency is reflected in the fact that only 300 cases have been reported worldwide.8 At birth, CMTC manifests as a pinkish reticulated pattern all over the body mimicking cutis marmorata; however, unlike cutis marmorata, the lesions do not improve with warming.9 The lesions of CMTC gradually lighten as the patient ages.8 Limb asymmetry is the most common extravascular complication of CMTC and, similar to SWS, glaucoma also can occur.10 Cutis marmorata telangiectatica congenita has been known to occur simultaneously with SWS or IH, but the combination of all 3 conditions in our patient is unique. Due to the scarcity of cases, the pathophysiology and treatment is poorly understood, with appropriate monitoring for sequelae recommended.9
Case Report
The patient was born at 39 weeks’ gestation following an uncomplicated pregnancy and delivery. She weighed 2950 g, her length was 19 in, and her head circumference was 13.25 in, correlating to the 10th, 50th, and 25th percentiles, respectively. Her Apgar score was 8/9 at 1 and 5 minutes. Her parents were nonconsanguineous and in good health. The patient’s family lived in poverty, which led us to conjecture about the role that toxins played in the epigenetics of the patient and her family. It was the mother’s third pregnancy; both prior pregnancies resulted in healthy children. The patient was breastfed. No family history of heritable vascular disorders was reported.
On the first day of life during the newborn examination, dark red pigment changes were noticed under the nose and erythematous pigmentation over the whole body was observed (Figure). On examination, 2-toned reticular lesions identified as extensive nevus flammeus were found bilaterally over the distribution of the ophthalmic division of the trigeminal nerve. A separate erythematous plaque over the maxilla also was recognized. The pediatrician suspected SWS and facial IH. The patient was discharged after 3 days with a referral to pediatric dermatology, and appropriate follow-up with a pediatrician was scheduled. The patient returned for these appointments and the significance of SWS was explained to her parents. Consultation with pediatric dermatology at 2 weeks of age confirmed the diagnosis of SWS as well as facial IH.
Upon further follow-up with pediatric dermatology at 2 months of age, the patient received an additional diagnosis of CMTC. These exceedingly rare lesions were located over the back, trunk, arms, and legs. The patient’s parents were counseled about the management of these conditions and appropriate follow-up.
Comment
This case describes 3 different vascular malformations in the same patient. Cutis marmorata telangiectatica congenita is rare and yet is described in this patient along with 2 other notable endothelial abnormalities. The clinical interest of this case is heightened by the presence of CMTC.
The causative factor of SWS is a well-documented mutation of the GNAQ gene, but there is considerable variability in how it affects the patient. Unlike in SWS, no single factor can be attributed to the development of IH. This case shows that these 3 diseases are not mutually exclusive and can present with unusually severe features when they occur concomitantly. The embryologic basis of SWS traces its roots back to the first trimester during vascular development, wher
The severity of the SWS in our patient was highlighted by the extensive nevus flammeus. These lesions occurred over the face, trunk, arms, and legs. The port-wine stain with dermatomal distribution of the ophthalmic nerve was the most concerning feature regarding the development of neurologic complications in this patient. Although the developmental delays associated with SWS can be serious, early intervention is important and can improve long-term outcomes. The facial IH arising at birth was contrary to the typical presentation. All of these factors will be kept in mind as the patient progresses and patient-centered care is provided. Because this patient’s presentation differed from other patients with IH, we will be more vigilant in providing close follow-up and monitoring for other medical problems involving other organs (eg, the brain); for instance, we will monitor for seizures and developmental delay.
Conclusion
In our patient, a unique pattern of SWS, facial IH, and CMTC are described in a pediatric patient. Many disciplines are involved in the treatment. In the patient’s first days of life, extensive collaboration between pediatrics and dermatologists was pivotal, with ophthalmology, pathology, and radiology consultations at hand. This case highlights that several vascular malformations of different origins can occur in the same patient. Epigenetic along with genetic factors likely contributed to this fascinating presentation. The importance of parental education and maintaining appropriate follow-up for this patient is crucial for a favorable outcome.
- Sinawat S, Auvichayapat N, Auvichayapat P, et al. 12-year retrospective study of Sturge-weber syndrome and literature review. J Med Assoc Thail. 2014;97:742-750.
- Shirley MD, Tang H, Gallione CJ, et al. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013;368:1971-1979.
- Sudarsanam A, Ardern-Holmes SL. Sturge-Weber syndrome: from the past to the present [published online November 7, 2013]. Eur J Paediat Neurol. 2014;18:257-266.
- Paller AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. Philadelphia, PA: Elsevier Saunders; 2011.
- Sujansky E, Conradi S. Sturge-Weber syndrome: age of onset of seizures and glaucoma and the prognosis for affected children. J Child Neurol. 1995;10:49-58.
- Lo W, Marchuk DA, Ball KL, et al. Updates and future horizons on the understanding, diagnosis, and treatment of Sturge-Weber syndrome brain involvement. Dev Med Child Neurol. 2012;54:214-223.
- Comi AM. Update on Sturge-Weber syndrome: diagnosis, treatment, quantitative measures, and controversies. Lymphat Res Biol. 2007;5:257-264.
- Resende CI, Araujo C, Vieira AP, et al. Cutis marmorata telangiectatica congenital [published online October 17, 2013]. BMJ Case Rep. doi:10.1136/bcr-2013-200056.
- Levy R, Lam JM. Cutis marmorata telangiectatica congenita: a mimicker of a common disorder. CMAJ. 2011;183:E249-E251.
- Kienast AK, Hoeger PH. Cutis marmorata telangiectatica congenita: a prospective study of 27 cases and review of the literature with proposal of diagnostic criteria. Clin Exp Dermatol. 2009;34:319-323.
- Comi AM. Topical review: pathophysiology of Sturge-Weber syndrome. J Child Neurol. 2003;18:509-516.
- Sinawat S, Auvichayapat N, Auvichayapat P, et al. 12-year retrospective study of Sturge-weber syndrome and literature review. J Med Assoc Thail. 2014;97:742-750.
- Shirley MD, Tang H, Gallione CJ, et al. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013;368:1971-1979.
- Sudarsanam A, Ardern-Holmes SL. Sturge-Weber syndrome: from the past to the present [published online November 7, 2013]. Eur J Paediat Neurol. 2014;18:257-266.
- Paller AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. Philadelphia, PA: Elsevier Saunders; 2011.
- Sujansky E, Conradi S. Sturge-Weber syndrome: age of onset of seizures and glaucoma and the prognosis for affected children. J Child Neurol. 1995;10:49-58.
- Lo W, Marchuk DA, Ball KL, et al. Updates and future horizons on the understanding, diagnosis, and treatment of Sturge-Weber syndrome brain involvement. Dev Med Child Neurol. 2012;54:214-223.
- Comi AM. Update on Sturge-Weber syndrome: diagnosis, treatment, quantitative measures, and controversies. Lymphat Res Biol. 2007;5:257-264.
- Resende CI, Araujo C, Vieira AP, et al. Cutis marmorata telangiectatica congenital [published online October 17, 2013]. BMJ Case Rep. doi:10.1136/bcr-2013-200056.
- Levy R, Lam JM. Cutis marmorata telangiectatica congenita: a mimicker of a common disorder. CMAJ. 2011;183:E249-E251.
- Kienast AK, Hoeger PH. Cutis marmorata telangiectatica congenita: a prospective study of 27 cases and review of the literature with proposal of diagnostic criteria. Clin Exp Dermatol. 2009;34:319-323.
- Comi AM. Topical review: pathophysiology of Sturge-Weber syndrome. J Child Neurol. 2003;18:509-516.
Practice Points
- This case highlights that several vascular malformations of different origins can occur in the same patient.
- Epigenetic factors along with genetic factors can lead to development of complex vascular conditions.
- Close collaborations of different medical specialties is necessary to make an accurate diagnosis and to follow up to achieve optimal long-term outcomes for patients with complex medical conditions.
