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Simple QI intervention helped improve HPV vaccination rates
TORONTO – Teaching simple quality improvement principles to individual pediatric practices can improve adolescent human papillomavirus (HPV) vaccination rates, results from a multicenter study showed.
“We know that HPV vaccination rates are low, and there have been many efforts to improve the vaccination rates nationwide,” one of the study authors, Manika Suryadevara, MD, said in an interview at the Pediatric Academic Societies meeting. “One reason that vaccine rates are low in adolescents is missed opportunities. Adolescents don’t always show up for routine well-child visits where immunization records are reviewed, but they may show up with a cold, a sprained ankle, or a hospital follow-up. Providers do not routinely check immunizations at these visits, then don’t recommend vaccine to those who need it. These are the missed opportunities we need to act upon.”
Data were entered into the AAP Quality Improvement Data Aggregator and run charts were printed. Next, each practice held monthly team meetings for 5 months to discuss chart review data, run chart results, and to determine intervention change for the next cycle. “Most of the interventions included standing orders, optimizing nurse’s visits, using electronic medical reminders to review immunization records, and having immunization records pulled for all adolescents who show up in their practice,” Dr. Suryadevara said. “The goal of these systematic changes is to make the work flow seamless.”
Analysis of run chart data revealed that over the five monthly cycles, the HPV vaccine completion rate improved from 45% to 65%, while the overall HPV vaccine missed opportunities was reduced from 45% to 19%. Specifically, reductions in missed opportunities fell from 9% to 0% during well-child visits, from 80% to 61% during acute visits, from 25% to 0% during follow-up visits, and from 11% to 0% during nurse-only visits. “We did see missed opportunities for acute visits – those who come in sick, but even these missed opportunities decreased over the 6-month study period,” Dr. Suryadevara said.
During follow-up teleconference calls, practice representatives reported positive experiences about the QI process and outcome improvements. “Once the practices were able to pull everyone on board and develop practice changes, I wasn’t surprised that the interventions worked,” she said. “They were able to develop systematic interventions, change the work flow in their practice, and get the results we anticipated.”
The study was funded by the AAP Hub and Spoke Initiative. Dr. Suryadevara reported having no financial disclosures.
dbrunk@mdedge.com
TORONTO – Teaching simple quality improvement principles to individual pediatric practices can improve adolescent human papillomavirus (HPV) vaccination rates, results from a multicenter study showed.
“We know that HPV vaccination rates are low, and there have been many efforts to improve the vaccination rates nationwide,” one of the study authors, Manika Suryadevara, MD, said in an interview at the Pediatric Academic Societies meeting. “One reason that vaccine rates are low in adolescents is missed opportunities. Adolescents don’t always show up for routine well-child visits where immunization records are reviewed, but they may show up with a cold, a sprained ankle, or a hospital follow-up. Providers do not routinely check immunizations at these visits, then don’t recommend vaccine to those who need it. These are the missed opportunities we need to act upon.”
Data were entered into the AAP Quality Improvement Data Aggregator and run charts were printed. Next, each practice held monthly team meetings for 5 months to discuss chart review data, run chart results, and to determine intervention change for the next cycle. “Most of the interventions included standing orders, optimizing nurse’s visits, using electronic medical reminders to review immunization records, and having immunization records pulled for all adolescents who show up in their practice,” Dr. Suryadevara said. “The goal of these systematic changes is to make the work flow seamless.”
Analysis of run chart data revealed that over the five monthly cycles, the HPV vaccine completion rate improved from 45% to 65%, while the overall HPV vaccine missed opportunities was reduced from 45% to 19%. Specifically, reductions in missed opportunities fell from 9% to 0% during well-child visits, from 80% to 61% during acute visits, from 25% to 0% during follow-up visits, and from 11% to 0% during nurse-only visits. “We did see missed opportunities for acute visits – those who come in sick, but even these missed opportunities decreased over the 6-month study period,” Dr. Suryadevara said.
During follow-up teleconference calls, practice representatives reported positive experiences about the QI process and outcome improvements. “Once the practices were able to pull everyone on board and develop practice changes, I wasn’t surprised that the interventions worked,” she said. “They were able to develop systematic interventions, change the work flow in their practice, and get the results we anticipated.”
The study was funded by the AAP Hub and Spoke Initiative. Dr. Suryadevara reported having no financial disclosures.
dbrunk@mdedge.com
TORONTO – Teaching simple quality improvement principles to individual pediatric practices can improve adolescent human papillomavirus (HPV) vaccination rates, results from a multicenter study showed.
“We know that HPV vaccination rates are low, and there have been many efforts to improve the vaccination rates nationwide,” one of the study authors, Manika Suryadevara, MD, said in an interview at the Pediatric Academic Societies meeting. “One reason that vaccine rates are low in adolescents is missed opportunities. Adolescents don’t always show up for routine well-child visits where immunization records are reviewed, but they may show up with a cold, a sprained ankle, or a hospital follow-up. Providers do not routinely check immunizations at these visits, then don’t recommend vaccine to those who need it. These are the missed opportunities we need to act upon.”
Data were entered into the AAP Quality Improvement Data Aggregator and run charts were printed. Next, each practice held monthly team meetings for 5 months to discuss chart review data, run chart results, and to determine intervention change for the next cycle. “Most of the interventions included standing orders, optimizing nurse’s visits, using electronic medical reminders to review immunization records, and having immunization records pulled for all adolescents who show up in their practice,” Dr. Suryadevara said. “The goal of these systematic changes is to make the work flow seamless.”
Analysis of run chart data revealed that over the five monthly cycles, the HPV vaccine completion rate improved from 45% to 65%, while the overall HPV vaccine missed opportunities was reduced from 45% to 19%. Specifically, reductions in missed opportunities fell from 9% to 0% during well-child visits, from 80% to 61% during acute visits, from 25% to 0% during follow-up visits, and from 11% to 0% during nurse-only visits. “We did see missed opportunities for acute visits – those who come in sick, but even these missed opportunities decreased over the 6-month study period,” Dr. Suryadevara said.
During follow-up teleconference calls, practice representatives reported positive experiences about the QI process and outcome improvements. “Once the practices were able to pull everyone on board and develop practice changes, I wasn’t surprised that the interventions worked,” she said. “They were able to develop systematic interventions, change the work flow in their practice, and get the results we anticipated.”
The study was funded by the AAP Hub and Spoke Initiative. Dr. Suryadevara reported having no financial disclosures.
dbrunk@mdedge.com
REPORTING FROM PAS 2018
Key clinical point: Teaching quality improvement to pediatric practices can improve adolescent human papillomavirus (HPV) vaccine completion rates.
Major finding:
Study details: A quality improvement project conducted at five large pediatric practices in New York state aimed at reducing missed vaccination opportunities in an effort to improve HPV vaccination completion rates.
Disclosures: The study was funded by the American Academy of Pediatrics Hub and Spoke Initiative. Dr. Suryadevara reported having no financial disclosures.
Regimen can improve DFS in newly diagnosed T-ALL
The addition of nelarabine can improve treatment outcomes for certain patients with T-cell acute lymphoblastic leukemia (T-ALL), according to a phase 3 trial.
Patients with newly diagnosed, intermediate- or high-risk T-ALL had a significant improvement in 4-year disease-free survival (DFS) if they received nelarabine in addition to chemotherapy and cranial irradiation.
The DFS benefit with nelarabine was significant for patients who received high-dose methotrexate but not for those who received escalating-dose methotrexate.
This study also included patients with T-cell lymphoblastic lymphoma (T-LL), and they did not experience an improvement in DFS with the addition of nelarabine.
Kimberly Dunsmore, MD, of Virginia Tech Carilion School of Medicine in Roanoke, presented these results in a press briefing in advance of the 2018 ASCO Annual Meeting. Additional results are scheduled to be presented at the meeting as abstract 10500.
This research was supported by the National Cancer Institute/National Institutes of Health and St. Baldrick’s Foundation. The researchers’ disclosures are listed with the abstract.
Patients and treatment
The trial enrolled 1895 patients, ages 1 to 30, who were newly diagnosed with T-ALL (94%) or T-LL (6%).
Patients received standard 4-drug induction chemotherapy, and 1307 of these patients were then randomized to 1 of 4 treatment arms.
Regardless of which arm they were randomized to, patients received an 11-drug chemotherapy regimen—the augmented Berlin-Frankfurt-Munster regimen. Intermediate- and high-risk patients in all 4 arms also received cranial irradiation.
In the first treatment arm, T-LL (n=58) and T-ALL (n=372) patients received escalating-dose methotrexate without leucovorin rescue and pegaspargase (C-MTX).
In the second treatment arm, patients with intermediate- and high-risk T-ALL (n=147) and T-LL (n=60) received C-MTX plus nelarabine (six 5-day courses at 650 mg/m2/day).
In the third arm, T-ALL patients (n=451) received high-dose methotrexate with leucovorin rescue (HD-MTX). T-LL patients were not eligible for this arm or the fourth treatment arm.
In the fourth arm, intermediate- and high-risk T-ALL patients (n=219) received HD-MTX and nelarabine (same schedule as above). This included 43 T-ALL patients who had induction failure and were assigned to this arm non-randomly.
Results
For T-ALL patients, the 4-year disease-free survival (DFS) rate was 84%, and the 4-year overall survival rate was 90%.
There was a significant improvement in DFS for T-ALL patients who received nelarabine compared to those who did not—89% and 83%, respectively (P=0.0332).
“Historically, about 80% of people [with T-ALL] live at least 4 years after being treated for their disease, but we felt we could and must do better,” Dr Dunsmore said. “Our trial shows that we could further increase survival rates by about 10%, which is very encouraging.”
Dr Dunsmore also noted that patients who received nelarabine had fewer central nervous system relapses.
Among T-ALL patients who received C-MTX, there was no significant difference in DFS for those who received nelarabine and those who did not—92% and 90%, respectively (P=0.3825).
However, for patients who received HD-MTX, the difference in DFS was significant. The DFS rate was 86% in patients who received nelarabine and 78% in those who did not (P=0.024).
For the T-ALL patients who failed induction and were assigned to HD-MTX and nelarabine, the 4-year DFS rate was 55%.
Patients with T-LL did not benefit from the addition of nelarabine. The 4-year DFS rate was 85% in the nelarabine recipients and 89% in non-recipients (P=0.2788).
There were no significant differences in overall toxicity or peripheral neurotoxicity between the treatment arms.
Dr Dunsmore said the next step with this research will be to examine the implications and potential benefits of using nelarabine in treatment protocols that do not include cranial radiation.
The addition of nelarabine can improve treatment outcomes for certain patients with T-cell acute lymphoblastic leukemia (T-ALL), according to a phase 3 trial.
Patients with newly diagnosed, intermediate- or high-risk T-ALL had a significant improvement in 4-year disease-free survival (DFS) if they received nelarabine in addition to chemotherapy and cranial irradiation.
The DFS benefit with nelarabine was significant for patients who received high-dose methotrexate but not for those who received escalating-dose methotrexate.
This study also included patients with T-cell lymphoblastic lymphoma (T-LL), and they did not experience an improvement in DFS with the addition of nelarabine.
Kimberly Dunsmore, MD, of Virginia Tech Carilion School of Medicine in Roanoke, presented these results in a press briefing in advance of the 2018 ASCO Annual Meeting. Additional results are scheduled to be presented at the meeting as abstract 10500.
This research was supported by the National Cancer Institute/National Institutes of Health and St. Baldrick’s Foundation. The researchers’ disclosures are listed with the abstract.
Patients and treatment
The trial enrolled 1895 patients, ages 1 to 30, who were newly diagnosed with T-ALL (94%) or T-LL (6%).
Patients received standard 4-drug induction chemotherapy, and 1307 of these patients were then randomized to 1 of 4 treatment arms.
Regardless of which arm they were randomized to, patients received an 11-drug chemotherapy regimen—the augmented Berlin-Frankfurt-Munster regimen. Intermediate- and high-risk patients in all 4 arms also received cranial irradiation.
In the first treatment arm, T-LL (n=58) and T-ALL (n=372) patients received escalating-dose methotrexate without leucovorin rescue and pegaspargase (C-MTX).
In the second treatment arm, patients with intermediate- and high-risk T-ALL (n=147) and T-LL (n=60) received C-MTX plus nelarabine (six 5-day courses at 650 mg/m2/day).
In the third arm, T-ALL patients (n=451) received high-dose methotrexate with leucovorin rescue (HD-MTX). T-LL patients were not eligible for this arm or the fourth treatment arm.
In the fourth arm, intermediate- and high-risk T-ALL patients (n=219) received HD-MTX and nelarabine (same schedule as above). This included 43 T-ALL patients who had induction failure and were assigned to this arm non-randomly.
Results
For T-ALL patients, the 4-year disease-free survival (DFS) rate was 84%, and the 4-year overall survival rate was 90%.
There was a significant improvement in DFS for T-ALL patients who received nelarabine compared to those who did not—89% and 83%, respectively (P=0.0332).
“Historically, about 80% of people [with T-ALL] live at least 4 years after being treated for their disease, but we felt we could and must do better,” Dr Dunsmore said. “Our trial shows that we could further increase survival rates by about 10%, which is very encouraging.”
Dr Dunsmore also noted that patients who received nelarabine had fewer central nervous system relapses.
Among T-ALL patients who received C-MTX, there was no significant difference in DFS for those who received nelarabine and those who did not—92% and 90%, respectively (P=0.3825).
However, for patients who received HD-MTX, the difference in DFS was significant. The DFS rate was 86% in patients who received nelarabine and 78% in those who did not (P=0.024).
For the T-ALL patients who failed induction and were assigned to HD-MTX and nelarabine, the 4-year DFS rate was 55%.
Patients with T-LL did not benefit from the addition of nelarabine. The 4-year DFS rate was 85% in the nelarabine recipients and 89% in non-recipients (P=0.2788).
There were no significant differences in overall toxicity or peripheral neurotoxicity between the treatment arms.
Dr Dunsmore said the next step with this research will be to examine the implications and potential benefits of using nelarabine in treatment protocols that do not include cranial radiation.
The addition of nelarabine can improve treatment outcomes for certain patients with T-cell acute lymphoblastic leukemia (T-ALL), according to a phase 3 trial.
Patients with newly diagnosed, intermediate- or high-risk T-ALL had a significant improvement in 4-year disease-free survival (DFS) if they received nelarabine in addition to chemotherapy and cranial irradiation.
The DFS benefit with nelarabine was significant for patients who received high-dose methotrexate but not for those who received escalating-dose methotrexate.
This study also included patients with T-cell lymphoblastic lymphoma (T-LL), and they did not experience an improvement in DFS with the addition of nelarabine.
Kimberly Dunsmore, MD, of Virginia Tech Carilion School of Medicine in Roanoke, presented these results in a press briefing in advance of the 2018 ASCO Annual Meeting. Additional results are scheduled to be presented at the meeting as abstract 10500.
This research was supported by the National Cancer Institute/National Institutes of Health and St. Baldrick’s Foundation. The researchers’ disclosures are listed with the abstract.
Patients and treatment
The trial enrolled 1895 patients, ages 1 to 30, who were newly diagnosed with T-ALL (94%) or T-LL (6%).
Patients received standard 4-drug induction chemotherapy, and 1307 of these patients were then randomized to 1 of 4 treatment arms.
Regardless of which arm they were randomized to, patients received an 11-drug chemotherapy regimen—the augmented Berlin-Frankfurt-Munster regimen. Intermediate- and high-risk patients in all 4 arms also received cranial irradiation.
In the first treatment arm, T-LL (n=58) and T-ALL (n=372) patients received escalating-dose methotrexate without leucovorin rescue and pegaspargase (C-MTX).
In the second treatment arm, patients with intermediate- and high-risk T-ALL (n=147) and T-LL (n=60) received C-MTX plus nelarabine (six 5-day courses at 650 mg/m2/day).
In the third arm, T-ALL patients (n=451) received high-dose methotrexate with leucovorin rescue (HD-MTX). T-LL patients were not eligible for this arm or the fourth treatment arm.
In the fourth arm, intermediate- and high-risk T-ALL patients (n=219) received HD-MTX and nelarabine (same schedule as above). This included 43 T-ALL patients who had induction failure and were assigned to this arm non-randomly.
Results
For T-ALL patients, the 4-year disease-free survival (DFS) rate was 84%, and the 4-year overall survival rate was 90%.
There was a significant improvement in DFS for T-ALL patients who received nelarabine compared to those who did not—89% and 83%, respectively (P=0.0332).
“Historically, about 80% of people [with T-ALL] live at least 4 years after being treated for their disease, but we felt we could and must do better,” Dr Dunsmore said. “Our trial shows that we could further increase survival rates by about 10%, which is very encouraging.”
Dr Dunsmore also noted that patients who received nelarabine had fewer central nervous system relapses.
Among T-ALL patients who received C-MTX, there was no significant difference in DFS for those who received nelarabine and those who did not—92% and 90%, respectively (P=0.3825).
However, for patients who received HD-MTX, the difference in DFS was significant. The DFS rate was 86% in patients who received nelarabine and 78% in those who did not (P=0.024).
For the T-ALL patients who failed induction and were assigned to HD-MTX and nelarabine, the 4-year DFS rate was 55%.
Patients with T-LL did not benefit from the addition of nelarabine. The 4-year DFS rate was 85% in the nelarabine recipients and 89% in non-recipients (P=0.2788).
There were no significant differences in overall toxicity or peripheral neurotoxicity between the treatment arms.
Dr Dunsmore said the next step with this research will be to examine the implications and potential benefits of using nelarabine in treatment protocols that do not include cranial radiation.
Which infants with invasive bacterial infections are at risk for adverse outcomes?
TORONTO – Among infants up to 60 days old with an invasive bacterial infection, adverse outcomes are associated with prematurity, ill appearance, and bacterial meningitis, a multicenter retrospective analysis found.
“Young infants are susceptible to serious bacterial infections, particularly when they’re less than 60 days of age,” Christopher Pruitt, MD, said at the annual Pediatric Academic Societies meeting. “Among these infants, bacteremia and bacterial meningitis, also referred to as invasive bacterial infections, are associated with higher rates of morbidity and mortality.”
The primary outcome measure was occurrence of an adverse clinical outcome within 30 days following the index ED visit. Adverse outcomes were defined as use of mechanical ventilation, vasoactive medications, any neurologic sequelae, and death. The researchers used a mixed-effects logistic regression model and retained covariates with a P value of less than .10. Covariates analyzed included age less than 28 days, prematurity, presence or absence of a complex chronic condition, presence of fever, ill appearance, bacterial meningitis, and concordant empiric antimicrobial therapy.
Of the 442 infants included in the final analysis, the majority (80%) had bacteremia, 14% had bacterial meningitis plus bacteremia, and 6% had bacterial meningitis only. “For purposes of this study, patients with bacterial meningitis with or without bacteremia were categorized as having bacterial meningitis,” Dr. Pruitt said. He and his associates found that 14.5% of infants had one or more adverse outcomes. Adverse outcomes occurred in 39% of infants with bacterial meningitis, compared with 8.2% of infants with isolated bacteremia. Need for mechanical ventilation, vasoactive medications, and neurologic disability also was more common among infants with bacterial meningitis than it was among children with isolated bacteremia. There were 10 deaths overall, which amounted to about 2% in both groups.
On multivariate analysis, the rate of adverse outcomes was significantly higher for patients with bacterial meningitis than it was for those with isolated bacteremia (adjusted odds ratio, 8.8), for premature versus term infants (AOR, 5.9), for infants who were ill appearing versus non-ill appearing (AOR, 3.9), and for infants with no fever versus those with fever (AOR, 2.4). No significant associations with 30-day adverse outcomes were seen in patients with a complex chronic condition, compared with those without a complex chronic condition (AOR, 2.0), nor in the those aged 29-60 days versus those younger than 29 days (15% vs. 14%, respectively; AOR 0.7).
“When looking at the most common scenario – a full-term infant without an ill appearance, and bacteremia as opposed to bacterial meningitis – 3 of these 219 infants, or 1.4%, had an adverse outcome,” said Dr. Pruitt, who cares for patients in the ED at Children’s of Alabama in Birmingham. “And there were no deaths.” He also reported that 12 infants with invasive bacterial infections were discharged from the index ED visit without antimicrobial treatment. All had bacteremia and none had an adverse outcome.
Dr. Pruitt acknowledged certain limitations of the study, including its retrospective design, that the outcomes were limited to 30 days, and the fact that the findings may not be generalizable to nontertiary settings. “Our findings have important implications for the care of infants with invasive bacterial infections,” he concluded. “In particular, the high rate of adverse outcomes for infants with bacterial meningitis can provide some context for clinicians in assessing the need for diagnostic evaluation for invasive bacterial infection and discussing testing and treatment with parents. Our findings may also help to inform inpatient management for hospitalized infants with invasive bacterial infections, as well as anticipatory guidance for parents, particularly around follow-up. Further prospective studies evaluating the long-term outcomes of infants with invasive bacterial infections are needed.”
The study was supported in part by a grant from the National Institutes of Health. Dr. Pruitt reported having no financial disclosures.
TORONTO – Among infants up to 60 days old with an invasive bacterial infection, adverse outcomes are associated with prematurity, ill appearance, and bacterial meningitis, a multicenter retrospective analysis found.
“Young infants are susceptible to serious bacterial infections, particularly when they’re less than 60 days of age,” Christopher Pruitt, MD, said at the annual Pediatric Academic Societies meeting. “Among these infants, bacteremia and bacterial meningitis, also referred to as invasive bacterial infections, are associated with higher rates of morbidity and mortality.”
The primary outcome measure was occurrence of an adverse clinical outcome within 30 days following the index ED visit. Adverse outcomes were defined as use of mechanical ventilation, vasoactive medications, any neurologic sequelae, and death. The researchers used a mixed-effects logistic regression model and retained covariates with a P value of less than .10. Covariates analyzed included age less than 28 days, prematurity, presence or absence of a complex chronic condition, presence of fever, ill appearance, bacterial meningitis, and concordant empiric antimicrobial therapy.
Of the 442 infants included in the final analysis, the majority (80%) had bacteremia, 14% had bacterial meningitis plus bacteremia, and 6% had bacterial meningitis only. “For purposes of this study, patients with bacterial meningitis with or without bacteremia were categorized as having bacterial meningitis,” Dr. Pruitt said. He and his associates found that 14.5% of infants had one or more adverse outcomes. Adverse outcomes occurred in 39% of infants with bacterial meningitis, compared with 8.2% of infants with isolated bacteremia. Need for mechanical ventilation, vasoactive medications, and neurologic disability also was more common among infants with bacterial meningitis than it was among children with isolated bacteremia. There were 10 deaths overall, which amounted to about 2% in both groups.
On multivariate analysis, the rate of adverse outcomes was significantly higher for patients with bacterial meningitis than it was for those with isolated bacteremia (adjusted odds ratio, 8.8), for premature versus term infants (AOR, 5.9), for infants who were ill appearing versus non-ill appearing (AOR, 3.9), and for infants with no fever versus those with fever (AOR, 2.4). No significant associations with 30-day adverse outcomes were seen in patients with a complex chronic condition, compared with those without a complex chronic condition (AOR, 2.0), nor in the those aged 29-60 days versus those younger than 29 days (15% vs. 14%, respectively; AOR 0.7).
“When looking at the most common scenario – a full-term infant without an ill appearance, and bacteremia as opposed to bacterial meningitis – 3 of these 219 infants, or 1.4%, had an adverse outcome,” said Dr. Pruitt, who cares for patients in the ED at Children’s of Alabama in Birmingham. “And there were no deaths.” He also reported that 12 infants with invasive bacterial infections were discharged from the index ED visit without antimicrobial treatment. All had bacteremia and none had an adverse outcome.
Dr. Pruitt acknowledged certain limitations of the study, including its retrospective design, that the outcomes were limited to 30 days, and the fact that the findings may not be generalizable to nontertiary settings. “Our findings have important implications for the care of infants with invasive bacterial infections,” he concluded. “In particular, the high rate of adverse outcomes for infants with bacterial meningitis can provide some context for clinicians in assessing the need for diagnostic evaluation for invasive bacterial infection and discussing testing and treatment with parents. Our findings may also help to inform inpatient management for hospitalized infants with invasive bacterial infections, as well as anticipatory guidance for parents, particularly around follow-up. Further prospective studies evaluating the long-term outcomes of infants with invasive bacterial infections are needed.”
The study was supported in part by a grant from the National Institutes of Health. Dr. Pruitt reported having no financial disclosures.
TORONTO – Among infants up to 60 days old with an invasive bacterial infection, adverse outcomes are associated with prematurity, ill appearance, and bacterial meningitis, a multicenter retrospective analysis found.
“Young infants are susceptible to serious bacterial infections, particularly when they’re less than 60 days of age,” Christopher Pruitt, MD, said at the annual Pediatric Academic Societies meeting. “Among these infants, bacteremia and bacterial meningitis, also referred to as invasive bacterial infections, are associated with higher rates of morbidity and mortality.”
The primary outcome measure was occurrence of an adverse clinical outcome within 30 days following the index ED visit. Adverse outcomes were defined as use of mechanical ventilation, vasoactive medications, any neurologic sequelae, and death. The researchers used a mixed-effects logistic regression model and retained covariates with a P value of less than .10. Covariates analyzed included age less than 28 days, prematurity, presence or absence of a complex chronic condition, presence of fever, ill appearance, bacterial meningitis, and concordant empiric antimicrobial therapy.
Of the 442 infants included in the final analysis, the majority (80%) had bacteremia, 14% had bacterial meningitis plus bacteremia, and 6% had bacterial meningitis only. “For purposes of this study, patients with bacterial meningitis with or without bacteremia were categorized as having bacterial meningitis,” Dr. Pruitt said. He and his associates found that 14.5% of infants had one or more adverse outcomes. Adverse outcomes occurred in 39% of infants with bacterial meningitis, compared with 8.2% of infants with isolated bacteremia. Need for mechanical ventilation, vasoactive medications, and neurologic disability also was more common among infants with bacterial meningitis than it was among children with isolated bacteremia. There were 10 deaths overall, which amounted to about 2% in both groups.
On multivariate analysis, the rate of adverse outcomes was significantly higher for patients with bacterial meningitis than it was for those with isolated bacteremia (adjusted odds ratio, 8.8), for premature versus term infants (AOR, 5.9), for infants who were ill appearing versus non-ill appearing (AOR, 3.9), and for infants with no fever versus those with fever (AOR, 2.4). No significant associations with 30-day adverse outcomes were seen in patients with a complex chronic condition, compared with those without a complex chronic condition (AOR, 2.0), nor in the those aged 29-60 days versus those younger than 29 days (15% vs. 14%, respectively; AOR 0.7).
“When looking at the most common scenario – a full-term infant without an ill appearance, and bacteremia as opposed to bacterial meningitis – 3 of these 219 infants, or 1.4%, had an adverse outcome,” said Dr. Pruitt, who cares for patients in the ED at Children’s of Alabama in Birmingham. “And there were no deaths.” He also reported that 12 infants with invasive bacterial infections were discharged from the index ED visit without antimicrobial treatment. All had bacteremia and none had an adverse outcome.
Dr. Pruitt acknowledged certain limitations of the study, including its retrospective design, that the outcomes were limited to 30 days, and the fact that the findings may not be generalizable to nontertiary settings. “Our findings have important implications for the care of infants with invasive bacterial infections,” he concluded. “In particular, the high rate of adverse outcomes for infants with bacterial meningitis can provide some context for clinicians in assessing the need for diagnostic evaluation for invasive bacterial infection and discussing testing and treatment with parents. Our findings may also help to inform inpatient management for hospitalized infants with invasive bacterial infections, as well as anticipatory guidance for parents, particularly around follow-up. Further prospective studies evaluating the long-term outcomes of infants with invasive bacterial infections are needed.”
The study was supported in part by a grant from the National Institutes of Health. Dr. Pruitt reported having no financial disclosures.
REPORTING FROM PAS 2018
Key clinical point:
Major finding: The rate of adverse outcomes was significantly higher for patients with bacterial meningitis versus those with isolated bacteremia (adjusted odds ratio, 8.8) and for premature versus term infants (AOR, 5.9).
Study details: A multicenter, retrospective review of 442 infants with invasive bacterial infections who were initially evaluated in the ED.
Disclosures: The study was supported in part by a grant from the National Institutes of Health. Dr. Pruitt reported having no financial disclosures.
Adolescent suicidal ideation and attempts are on the rise
according to a retrospective analysis by Gregory Plemmons, MD, of Vanderbilt University, Nashville, Tenn., and his coinvestigators.
The researchers also found that suicidal ideation and suicide attempts occurred more often during the spring and fall than in the summer, coinciding with the academic school year, highlighting “the need for further research in the role that schools may play.”
The investigators distinguished three age groups corresponding with commonly accepted definitions of late childhood (5-11 years), early adolescence (12-14 years), and late adolescence (15-17 years). They also looked at differences according to patients’ race/ethnicity and sex, as well as month of the year of the admission.
There were increases in suicidal ideation or attempts across all three age groups, with 50% in late adolescence, 37% in early adolescence, and 13% in late childhood. They also found higher increases among non-Hispanic whites, compared with other races; nearly two-thirds of the suicidal ideation and suicide attempts were among girls.
Only 18.5% of total annual suicidal ideation and suicidal attempts occurred during summer months. Peaks were highest in fall and spring. “We underscore the need for future work to explore the relationship between school and suicidal ideation, recognizing that the role of academics is a complex one, and there may also be other additional influences at play regarding seasonality,” said Dr. Plemmons and his associates.
The investigators wrote that, although the reasons for these increasing trends among these age groups are not entirely clear, some have suggested the rise of cyberbullying and social media could be possible factors. This study and its data, though, “have important implications for exploring age- and sex-specific approaches to suicide screening and prevention interventions, as well as further research in examining causal factors for SI [suicidal ideation] and SA [suicide attempts],” they concluded.
SOURCE: Plemmons G et al. Pediatrics. 2018;141(6):e20172426.
according to a retrospective analysis by Gregory Plemmons, MD, of Vanderbilt University, Nashville, Tenn., and his coinvestigators.
The researchers also found that suicidal ideation and suicide attempts occurred more often during the spring and fall than in the summer, coinciding with the academic school year, highlighting “the need for further research in the role that schools may play.”
The investigators distinguished three age groups corresponding with commonly accepted definitions of late childhood (5-11 years), early adolescence (12-14 years), and late adolescence (15-17 years). They also looked at differences according to patients’ race/ethnicity and sex, as well as month of the year of the admission.
There were increases in suicidal ideation or attempts across all three age groups, with 50% in late adolescence, 37% in early adolescence, and 13% in late childhood. They also found higher increases among non-Hispanic whites, compared with other races; nearly two-thirds of the suicidal ideation and suicide attempts were among girls.
Only 18.5% of total annual suicidal ideation and suicidal attempts occurred during summer months. Peaks were highest in fall and spring. “We underscore the need for future work to explore the relationship between school and suicidal ideation, recognizing that the role of academics is a complex one, and there may also be other additional influences at play regarding seasonality,” said Dr. Plemmons and his associates.
The investigators wrote that, although the reasons for these increasing trends among these age groups are not entirely clear, some have suggested the rise of cyberbullying and social media could be possible factors. This study and its data, though, “have important implications for exploring age- and sex-specific approaches to suicide screening and prevention interventions, as well as further research in examining causal factors for SI [suicidal ideation] and SA [suicide attempts],” they concluded.
SOURCE: Plemmons G et al. Pediatrics. 2018;141(6):e20172426.
according to a retrospective analysis by Gregory Plemmons, MD, of Vanderbilt University, Nashville, Tenn., and his coinvestigators.
The researchers also found that suicidal ideation and suicide attempts occurred more often during the spring and fall than in the summer, coinciding with the academic school year, highlighting “the need for further research in the role that schools may play.”
The investigators distinguished three age groups corresponding with commonly accepted definitions of late childhood (5-11 years), early adolescence (12-14 years), and late adolescence (15-17 years). They also looked at differences according to patients’ race/ethnicity and sex, as well as month of the year of the admission.
There were increases in suicidal ideation or attempts across all three age groups, with 50% in late adolescence, 37% in early adolescence, and 13% in late childhood. They also found higher increases among non-Hispanic whites, compared with other races; nearly two-thirds of the suicidal ideation and suicide attempts were among girls.
Only 18.5% of total annual suicidal ideation and suicidal attempts occurred during summer months. Peaks were highest in fall and spring. “We underscore the need for future work to explore the relationship between school and suicidal ideation, recognizing that the role of academics is a complex one, and there may also be other additional influences at play regarding seasonality,” said Dr. Plemmons and his associates.
The investigators wrote that, although the reasons for these increasing trends among these age groups are not entirely clear, some have suggested the rise of cyberbullying and social media could be possible factors. This study and its data, though, “have important implications for exploring age- and sex-specific approaches to suicide screening and prevention interventions, as well as further research in examining causal factors for SI [suicidal ideation] and SA [suicide attempts],” they concluded.
SOURCE: Plemmons G et al. Pediatrics. 2018;141(6):e20172426.
FROM PEDIATRICS
Carotenoderma Associated With a Diet Rich in Red Palm Oil
To the Editor:
Carotenoderma is a cutaneous manifestation of elevated serum β-carotene levels and classically localizes to fatty tissues and areas rich in sweat glands. We present a case of carotenoderma associated with a diet rich in red palm oil, a common food additive in parts of the world outside of the United States.
A previously healthy 8-year-old boy who recently immigrated to the United States from Liberia was hospitalized for treatment of a febrile illness that subsequently was attributed to a viral syndrome. On physical examination by the dermatology department, the patient was noted to have marked orange discoloration on the palms and soles (Figure). Laboratory workup revealed elevated serum β-carotene levels of 809 μg/dL (reference range, 10–85 μg/dL). Testing of hemoglobin/hematocrit levels and liver, thyroid, and kidney function was normal, and systemic examination revealed no further abnormalities. Upon further inquiry by the dermatology department, the patient’s family reported frequent addition of red palm oil to all of the child’s meals. The patient subsequently was diagnosed with carotenoderma and was instructed to limit inclusion of red palm oil in his diet.
Red palm oil is a rich source of β-carotene and is commonly used outside the United States as a dietary supplement or food flavoring. Excessive consumption of red palm oil or other sources rich in carotenes can result in elevated serum carotene levels or hypercarotenemia. An elevation in serum β-carotene levels may be recognized from 4 to 7 weeks after starting a β-carotene–rich diet.1
While dietary consumption of carotenes is the most common cause of carotenoderma, others include kidney or liver disease, hyperlipidemia, porphyria, diabetes mellitus, hypothyroidism, and anorexia nervosa.2-4 Moreover, since carotenoids are enzymatically converted to vitamin A in the small intestine, a mutation of the gene of the conversion enzyme β-carotene 15,15’-monooxygenase 1 (BCMO1) also can cause be a rare cause of hypercarotenemia.3
Carotenoderma, the clinical cutaneous manifestation of hypercarotenemia, occurs as a result of β-carotene deposits in the skin when serum concentration exceeds 250 μg/dL. More specifically, β-carotene accumulates mainly in the lipid-rich stratum corneum as well as in sweat and sebum, which explains the localized discoloration in fatty tissues and areas rich in sweat glands (eg, nasolabial folds, palms, soles).3,4 The sclerae of the eyes are not affected by the surplus of β-carotene in carotenoderma, which helps distinguish it from jaundice.5
The differential diagnosis of yellow discoloration of the skin includes jaundice, encompassing the prehepatic, hepatocellular, and posthepatic categories.4 Also noteworthy in the differential diagnosis is lycopenemia, which occurs as a result of eating lycopene-rich foods (eg, tomatoes), resulting in a deeper orange-yellow pigmentation when compared to the cutaneous manifestation of hypercarotenemia.2,4,6 Several drugs also have been reported to induce yellow discoloration of the skin, including sunitinib,7 sorafenib,8 quinacrine, saffron supplements, santonin, fluorescein, 2,4-dinitrophenol, canthaxanthin, tetryl and picric acids, and acriflavine.2,4
Carotenoderma caused by a diet rich in β-carotene is a benign condition in which a diet low in β-carotene is implicated for treatment. Contrary to popular belief, vitamin A toxicity does not occur in the presence of a surplus of β-carotenes because the enzymatic conversion of β-carotene to vitamin A is strictly regulated.9 Although acknowledging the various causes of carotenoderma is important, a simple history and laboratory testing for elevated serum β-carotene levels can eliminate further unnecessary testing and allow for prompt recognition of the condition. Appropriate dietary modifications also may be warranted.
- Roe DA. Assessment of risk factors for carotenodermia and cutaneous signs of hypervitaminosis A in college-aged populations. Semin Dermatol. 1991;10:303-308.
- Manolios N, Samaras K. Hypercarotenaemia. Intern Med J. 2006;36:534.
- Wageesha ND, Ekanayake S, Jansz ER, et al. Studies on hypercarotenemia due to excessive ingestion of carrot, pumpkin and papaw [published online September 27, 2010]. Int J Food Sci Nutr. 2011;62:20-25.
- Maharshak N, Shapiro J, Trau H. Carotenoderma—a review of the current literature. Int J Dermatol. 2003;42:178-181.
- Maruani A, Labarthe F, Dupré T, et al. Hypercarotenaemia in an infant [in French]. Ann Dermatol Venereol. 2010;137:32-35.
- Shaw JA, Koti M. Clinical images. CMAJ. 2009;180:895.
- Vignand-Courtin C, Martin C, Le Beller C, et al. Cutaneous side effects associated with sunitinib: an analysis of 8 cases. Int J Clin Pharm. 2012;34:286-289.
- Dasanu CA, Alexandrescu DT, Dutcher J. Yellow skin discoloration associated with sorafenib use for treatment of metastatic renal cell carcinoma. South Med J. 2007;100:328-330.
- Lascari AD. Carotenemia. a review. Clin Pediatr (Phila). 1981;20:25-29.
To the Editor:
Carotenoderma is a cutaneous manifestation of elevated serum β-carotene levels and classically localizes to fatty tissues and areas rich in sweat glands. We present a case of carotenoderma associated with a diet rich in red palm oil, a common food additive in parts of the world outside of the United States.
A previously healthy 8-year-old boy who recently immigrated to the United States from Liberia was hospitalized for treatment of a febrile illness that subsequently was attributed to a viral syndrome. On physical examination by the dermatology department, the patient was noted to have marked orange discoloration on the palms and soles (Figure). Laboratory workup revealed elevated serum β-carotene levels of 809 μg/dL (reference range, 10–85 μg/dL). Testing of hemoglobin/hematocrit levels and liver, thyroid, and kidney function was normal, and systemic examination revealed no further abnormalities. Upon further inquiry by the dermatology department, the patient’s family reported frequent addition of red palm oil to all of the child’s meals. The patient subsequently was diagnosed with carotenoderma and was instructed to limit inclusion of red palm oil in his diet.
Red palm oil is a rich source of β-carotene and is commonly used outside the United States as a dietary supplement or food flavoring. Excessive consumption of red palm oil or other sources rich in carotenes can result in elevated serum carotene levels or hypercarotenemia. An elevation in serum β-carotene levels may be recognized from 4 to 7 weeks after starting a β-carotene–rich diet.1
While dietary consumption of carotenes is the most common cause of carotenoderma, others include kidney or liver disease, hyperlipidemia, porphyria, diabetes mellitus, hypothyroidism, and anorexia nervosa.2-4 Moreover, since carotenoids are enzymatically converted to vitamin A in the small intestine, a mutation of the gene of the conversion enzyme β-carotene 15,15’-monooxygenase 1 (BCMO1) also can cause be a rare cause of hypercarotenemia.3
Carotenoderma, the clinical cutaneous manifestation of hypercarotenemia, occurs as a result of β-carotene deposits in the skin when serum concentration exceeds 250 μg/dL. More specifically, β-carotene accumulates mainly in the lipid-rich stratum corneum as well as in sweat and sebum, which explains the localized discoloration in fatty tissues and areas rich in sweat glands (eg, nasolabial folds, palms, soles).3,4 The sclerae of the eyes are not affected by the surplus of β-carotene in carotenoderma, which helps distinguish it from jaundice.5
The differential diagnosis of yellow discoloration of the skin includes jaundice, encompassing the prehepatic, hepatocellular, and posthepatic categories.4 Also noteworthy in the differential diagnosis is lycopenemia, which occurs as a result of eating lycopene-rich foods (eg, tomatoes), resulting in a deeper orange-yellow pigmentation when compared to the cutaneous manifestation of hypercarotenemia.2,4,6 Several drugs also have been reported to induce yellow discoloration of the skin, including sunitinib,7 sorafenib,8 quinacrine, saffron supplements, santonin, fluorescein, 2,4-dinitrophenol, canthaxanthin, tetryl and picric acids, and acriflavine.2,4
Carotenoderma caused by a diet rich in β-carotene is a benign condition in which a diet low in β-carotene is implicated for treatment. Contrary to popular belief, vitamin A toxicity does not occur in the presence of a surplus of β-carotenes because the enzymatic conversion of β-carotene to vitamin A is strictly regulated.9 Although acknowledging the various causes of carotenoderma is important, a simple history and laboratory testing for elevated serum β-carotene levels can eliminate further unnecessary testing and allow for prompt recognition of the condition. Appropriate dietary modifications also may be warranted.
To the Editor:
Carotenoderma is a cutaneous manifestation of elevated serum β-carotene levels and classically localizes to fatty tissues and areas rich in sweat glands. We present a case of carotenoderma associated with a diet rich in red palm oil, a common food additive in parts of the world outside of the United States.
A previously healthy 8-year-old boy who recently immigrated to the United States from Liberia was hospitalized for treatment of a febrile illness that subsequently was attributed to a viral syndrome. On physical examination by the dermatology department, the patient was noted to have marked orange discoloration on the palms and soles (Figure). Laboratory workup revealed elevated serum β-carotene levels of 809 μg/dL (reference range, 10–85 μg/dL). Testing of hemoglobin/hematocrit levels and liver, thyroid, and kidney function was normal, and systemic examination revealed no further abnormalities. Upon further inquiry by the dermatology department, the patient’s family reported frequent addition of red palm oil to all of the child’s meals. The patient subsequently was diagnosed with carotenoderma and was instructed to limit inclusion of red palm oil in his diet.
Red palm oil is a rich source of β-carotene and is commonly used outside the United States as a dietary supplement or food flavoring. Excessive consumption of red palm oil or other sources rich in carotenes can result in elevated serum carotene levels or hypercarotenemia. An elevation in serum β-carotene levels may be recognized from 4 to 7 weeks after starting a β-carotene–rich diet.1
While dietary consumption of carotenes is the most common cause of carotenoderma, others include kidney or liver disease, hyperlipidemia, porphyria, diabetes mellitus, hypothyroidism, and anorexia nervosa.2-4 Moreover, since carotenoids are enzymatically converted to vitamin A in the small intestine, a mutation of the gene of the conversion enzyme β-carotene 15,15’-monooxygenase 1 (BCMO1) also can cause be a rare cause of hypercarotenemia.3
Carotenoderma, the clinical cutaneous manifestation of hypercarotenemia, occurs as a result of β-carotene deposits in the skin when serum concentration exceeds 250 μg/dL. More specifically, β-carotene accumulates mainly in the lipid-rich stratum corneum as well as in sweat and sebum, which explains the localized discoloration in fatty tissues and areas rich in sweat glands (eg, nasolabial folds, palms, soles).3,4 The sclerae of the eyes are not affected by the surplus of β-carotene in carotenoderma, which helps distinguish it from jaundice.5
The differential diagnosis of yellow discoloration of the skin includes jaundice, encompassing the prehepatic, hepatocellular, and posthepatic categories.4 Also noteworthy in the differential diagnosis is lycopenemia, which occurs as a result of eating lycopene-rich foods (eg, tomatoes), resulting in a deeper orange-yellow pigmentation when compared to the cutaneous manifestation of hypercarotenemia.2,4,6 Several drugs also have been reported to induce yellow discoloration of the skin, including sunitinib,7 sorafenib,8 quinacrine, saffron supplements, santonin, fluorescein, 2,4-dinitrophenol, canthaxanthin, tetryl and picric acids, and acriflavine.2,4
Carotenoderma caused by a diet rich in β-carotene is a benign condition in which a diet low in β-carotene is implicated for treatment. Contrary to popular belief, vitamin A toxicity does not occur in the presence of a surplus of β-carotenes because the enzymatic conversion of β-carotene to vitamin A is strictly regulated.9 Although acknowledging the various causes of carotenoderma is important, a simple history and laboratory testing for elevated serum β-carotene levels can eliminate further unnecessary testing and allow for prompt recognition of the condition. Appropriate dietary modifications also may be warranted.
- Roe DA. Assessment of risk factors for carotenodermia and cutaneous signs of hypervitaminosis A in college-aged populations. Semin Dermatol. 1991;10:303-308.
- Manolios N, Samaras K. Hypercarotenaemia. Intern Med J. 2006;36:534.
- Wageesha ND, Ekanayake S, Jansz ER, et al. Studies on hypercarotenemia due to excessive ingestion of carrot, pumpkin and papaw [published online September 27, 2010]. Int J Food Sci Nutr. 2011;62:20-25.
- Maharshak N, Shapiro J, Trau H. Carotenoderma—a review of the current literature. Int J Dermatol. 2003;42:178-181.
- Maruani A, Labarthe F, Dupré T, et al. Hypercarotenaemia in an infant [in French]. Ann Dermatol Venereol. 2010;137:32-35.
- Shaw JA, Koti M. Clinical images. CMAJ. 2009;180:895.
- Vignand-Courtin C, Martin C, Le Beller C, et al. Cutaneous side effects associated with sunitinib: an analysis of 8 cases. Int J Clin Pharm. 2012;34:286-289.
- Dasanu CA, Alexandrescu DT, Dutcher J. Yellow skin discoloration associated with sorafenib use for treatment of metastatic renal cell carcinoma. South Med J. 2007;100:328-330.
- Lascari AD. Carotenemia. a review. Clin Pediatr (Phila). 1981;20:25-29.
- Roe DA. Assessment of risk factors for carotenodermia and cutaneous signs of hypervitaminosis A in college-aged populations. Semin Dermatol. 1991;10:303-308.
- Manolios N, Samaras K. Hypercarotenaemia. Intern Med J. 2006;36:534.
- Wageesha ND, Ekanayake S, Jansz ER, et al. Studies on hypercarotenemia due to excessive ingestion of carrot, pumpkin and papaw [published online September 27, 2010]. Int J Food Sci Nutr. 2011;62:20-25.
- Maharshak N, Shapiro J, Trau H. Carotenoderma—a review of the current literature. Int J Dermatol. 2003;42:178-181.
- Maruani A, Labarthe F, Dupré T, et al. Hypercarotenaemia in an infant [in French]. Ann Dermatol Venereol. 2010;137:32-35.
- Shaw JA, Koti M. Clinical images. CMAJ. 2009;180:895.
- Vignand-Courtin C, Martin C, Le Beller C, et al. Cutaneous side effects associated with sunitinib: an analysis of 8 cases. Int J Clin Pharm. 2012;34:286-289.
- Dasanu CA, Alexandrescu DT, Dutcher J. Yellow skin discoloration associated with sorafenib use for treatment of metastatic renal cell carcinoma. South Med J. 2007;100:328-330.
- Lascari AD. Carotenemia. a review. Clin Pediatr (Phila). 1981;20:25-29.
Practice Points
- Carotenoderma is a cutaneous manifestation of elevated serum β-carotene levels and classically localizes to fatty tissues and areas rich in sweat glands.
- Carotenoderma caused by a diet rich in β-carotene is a benign condition in which a diet low in β-carotene is implicated for treatment.
Hyperpigmentation, paraparesis are signs of vitamin B12 deficiency
Vitamin B12 deficiency can cause skin hyperpigmentation and partial paralysis, but these issues can be easily treated early on with vitamin B12 shots, said Ashish Agarwal, MD, and his colleagues at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.
A 6-year-old boy, who had been previously healthy, presented with darkening of his hands and feet over a 4-month period. It also was noted that the skin on his palms and soles was thin and shiny. His walking gait had become abnormal in the previous 2 weeks; his legs were stiff when he walked, which caused him to fall and led to difficulty climbing stairs. The boy had no personal or family history of muscle issues or neurological issues. The boy’s personal history revealed that he ate a vegetarian diet.
A clinical diagnosis was made of megaloblastic anemia with subacute degeneration of the cord caused by vitamin B12 deficiency, a diagnosis not uncommon among vegetarians. The boy was started on daily intramuscular injections of B12 for 2 weeks, followed by weekly injections for a month. Monthly injections then were administered for the next 2 months. In the first few weeks, the hyperpigmentation began improving. At his 4-month follow-up, the boy was asymptomatic with reversal of the hyperpigmentation.
Dr. Agarwal and his associates concluded that skin darkening is an important clue toward underlying hematologic and neurologic manifestations of B12 deficiency.
SOURCE: Agarwal A et al. J Pediatr. 2018. doi: 10.1016/j.jpeds.2018.03.073.
Vitamin B12 deficiency can cause skin hyperpigmentation and partial paralysis, but these issues can be easily treated early on with vitamin B12 shots, said Ashish Agarwal, MD, and his colleagues at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.
A 6-year-old boy, who had been previously healthy, presented with darkening of his hands and feet over a 4-month period. It also was noted that the skin on his palms and soles was thin and shiny. His walking gait had become abnormal in the previous 2 weeks; his legs were stiff when he walked, which caused him to fall and led to difficulty climbing stairs. The boy had no personal or family history of muscle issues or neurological issues. The boy’s personal history revealed that he ate a vegetarian diet.
A clinical diagnosis was made of megaloblastic anemia with subacute degeneration of the cord caused by vitamin B12 deficiency, a diagnosis not uncommon among vegetarians. The boy was started on daily intramuscular injections of B12 for 2 weeks, followed by weekly injections for a month. Monthly injections then were administered for the next 2 months. In the first few weeks, the hyperpigmentation began improving. At his 4-month follow-up, the boy was asymptomatic with reversal of the hyperpigmentation.
Dr. Agarwal and his associates concluded that skin darkening is an important clue toward underlying hematologic and neurologic manifestations of B12 deficiency.
SOURCE: Agarwal A et al. J Pediatr. 2018. doi: 10.1016/j.jpeds.2018.03.073.
Vitamin B12 deficiency can cause skin hyperpigmentation and partial paralysis, but these issues can be easily treated early on with vitamin B12 shots, said Ashish Agarwal, MD, and his colleagues at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.
A 6-year-old boy, who had been previously healthy, presented with darkening of his hands and feet over a 4-month period. It also was noted that the skin on his palms and soles was thin and shiny. His walking gait had become abnormal in the previous 2 weeks; his legs were stiff when he walked, which caused him to fall and led to difficulty climbing stairs. The boy had no personal or family history of muscle issues or neurological issues. The boy’s personal history revealed that he ate a vegetarian diet.
A clinical diagnosis was made of megaloblastic anemia with subacute degeneration of the cord caused by vitamin B12 deficiency, a diagnosis not uncommon among vegetarians. The boy was started on daily intramuscular injections of B12 for 2 weeks, followed by weekly injections for a month. Monthly injections then were administered for the next 2 months. In the first few weeks, the hyperpigmentation began improving. At his 4-month follow-up, the boy was asymptomatic with reversal of the hyperpigmentation.
Dr. Agarwal and his associates concluded that skin darkening is an important clue toward underlying hematologic and neurologic manifestations of B12 deficiency.
SOURCE: Agarwal A et al. J Pediatr. 2018. doi: 10.1016/j.jpeds.2018.03.073.
FROM THE JOURNAL OF PEDIATRICS
Babies exposed to SSRIs in utero have decreased LV size
TORONTO – according to a small study presented at the Pediatric Academic Societies annual meeting.
“Given the frequency of SSRI use during pregnancy and continued conflicting results regarding cardiac effects, it is an important area of study,” senior author Sarah Haskell, DO, said in an interview. Her group at the University of Iowa in Coralville, which includes first author Deidra Ansah, MD, previously demonstrated reduced ventricular size and cardiac function in sertraline-exposed animal models.
Compared with unexposed newborns, SSRI-exposed infants had a 16% reduction in right ventricular (RV) diameter in diastole (P = .02) and a 22% reduction in left ventricular (LV) volume in systole (P = .02). They also had decreased LV lengths in diastole and systole (P = .045 and .004, respectively), but no impact was noted on cardiac function, as measured by shortening fraction.
“While cardiac function was appropriate on the initial echocardiogram, there were significant differences in cardiac dimensions,” said Dr. Haskell. “Whether these differences influence health and disease susceptibility requires further, longer-term studies.”
Her group plans to continue investigating the effects of SSRIs on cardiac development and also plans to study the offspring of women who are depressed but not on pharmacologic treatment to determine the effects of depression alone on cardiac size and function.
Dr. Haskell and her colleagues studied 21 term infants without and 20 term infants with exposure to in utero SSRIs who underwent standard echocardiograms including four-chamber and M-mode views within 48 hours of life. Exclusion criteria included prematurity, large or small for gestational age, any respiratory or cardiac support, and any major congenital malformations.
The mothers of exposed infants had higher depression scores compared with controls (P = .004), and had minimal to mild depression. Otherwise, they were similar in terms of age, weight, and likelihood of having chronic or gestational hypertension or diabetes. There also were no differences in maternal conditions or infant birth weight, body surface area or gestational age.
In the infants, no differences were seen in the occurrence of patent foramen ovale, patent ductus arteriosus, ventricular septal defect, or peripheral pulmonary artery stenosis.
This research was supported by the Department of Pediatric K12 Child Health Research Career Development Award, the Stead Family Department of Pediatrics at the University of Iowa, an NIH T32 grant, and the Children’s Miracle Network. The authors reported no financial disclosures.
TORONTO – according to a small study presented at the Pediatric Academic Societies annual meeting.
“Given the frequency of SSRI use during pregnancy and continued conflicting results regarding cardiac effects, it is an important area of study,” senior author Sarah Haskell, DO, said in an interview. Her group at the University of Iowa in Coralville, which includes first author Deidra Ansah, MD, previously demonstrated reduced ventricular size and cardiac function in sertraline-exposed animal models.
Compared with unexposed newborns, SSRI-exposed infants had a 16% reduction in right ventricular (RV) diameter in diastole (P = .02) and a 22% reduction in left ventricular (LV) volume in systole (P = .02). They also had decreased LV lengths in diastole and systole (P = .045 and .004, respectively), but no impact was noted on cardiac function, as measured by shortening fraction.
“While cardiac function was appropriate on the initial echocardiogram, there were significant differences in cardiac dimensions,” said Dr. Haskell. “Whether these differences influence health and disease susceptibility requires further, longer-term studies.”
Her group plans to continue investigating the effects of SSRIs on cardiac development and also plans to study the offspring of women who are depressed but not on pharmacologic treatment to determine the effects of depression alone on cardiac size and function.
Dr. Haskell and her colleagues studied 21 term infants without and 20 term infants with exposure to in utero SSRIs who underwent standard echocardiograms including four-chamber and M-mode views within 48 hours of life. Exclusion criteria included prematurity, large or small for gestational age, any respiratory or cardiac support, and any major congenital malformations.
The mothers of exposed infants had higher depression scores compared with controls (P = .004), and had minimal to mild depression. Otherwise, they were similar in terms of age, weight, and likelihood of having chronic or gestational hypertension or diabetes. There also were no differences in maternal conditions or infant birth weight, body surface area or gestational age.
In the infants, no differences were seen in the occurrence of patent foramen ovale, patent ductus arteriosus, ventricular septal defect, or peripheral pulmonary artery stenosis.
This research was supported by the Department of Pediatric K12 Child Health Research Career Development Award, the Stead Family Department of Pediatrics at the University of Iowa, an NIH T32 grant, and the Children’s Miracle Network. The authors reported no financial disclosures.
TORONTO – according to a small study presented at the Pediatric Academic Societies annual meeting.
“Given the frequency of SSRI use during pregnancy and continued conflicting results regarding cardiac effects, it is an important area of study,” senior author Sarah Haskell, DO, said in an interview. Her group at the University of Iowa in Coralville, which includes first author Deidra Ansah, MD, previously demonstrated reduced ventricular size and cardiac function in sertraline-exposed animal models.
Compared with unexposed newborns, SSRI-exposed infants had a 16% reduction in right ventricular (RV) diameter in diastole (P = .02) and a 22% reduction in left ventricular (LV) volume in systole (P = .02). They also had decreased LV lengths in diastole and systole (P = .045 and .004, respectively), but no impact was noted on cardiac function, as measured by shortening fraction.
“While cardiac function was appropriate on the initial echocardiogram, there were significant differences in cardiac dimensions,” said Dr. Haskell. “Whether these differences influence health and disease susceptibility requires further, longer-term studies.”
Her group plans to continue investigating the effects of SSRIs on cardiac development and also plans to study the offspring of women who are depressed but not on pharmacologic treatment to determine the effects of depression alone on cardiac size and function.
Dr. Haskell and her colleagues studied 21 term infants without and 20 term infants with exposure to in utero SSRIs who underwent standard echocardiograms including four-chamber and M-mode views within 48 hours of life. Exclusion criteria included prematurity, large or small for gestational age, any respiratory or cardiac support, and any major congenital malformations.
The mothers of exposed infants had higher depression scores compared with controls (P = .004), and had minimal to mild depression. Otherwise, they were similar in terms of age, weight, and likelihood of having chronic or gestational hypertension or diabetes. There also were no differences in maternal conditions or infant birth weight, body surface area or gestational age.
In the infants, no differences were seen in the occurrence of patent foramen ovale, patent ductus arteriosus, ventricular septal defect, or peripheral pulmonary artery stenosis.
This research was supported by the Department of Pediatric K12 Child Health Research Career Development Award, the Stead Family Department of Pediatrics at the University of Iowa, an NIH T32 grant, and the Children’s Miracle Network. The authors reported no financial disclosures.
AT PAS 2018
Key clinical point: Babies exposed to SSRIs in utero have smaller hearts compared with babies not exposed to SSRIs.
Major finding: Compared with unexposed newborns, SSRI-exposed infants had a 16% reduction in right ventricular diameter in diastole (P = .02) and a 22% reduction in left ventricular volume in systole (P = .02).
Study details: A study of 20 babies exposed to SSRIs in utero and 21 not exposed.
Disclosures: This research was supported by the Department of Pediatric K12 Child Health Research Career Development Award, the Stead Family Department of Pediatrics at the University of Iowa, an NIH T32 grant, and the Children’s Miracle Network. The authors reported no financial disclosures.
Persistent providers sway parents to accept HPV vaccination
according to data from 43 pediatrician clinic visits at six clinics in Texas.
Vaccine hesitancy is on the rise among parents in the United States, wrote Laura A. Shay, PhD, of the University of Texas School of Public Health, San Antonio, and her colleagues. “Although vaccine hesitancy is subject to influence, to our knowledge, no authors of previous studies have analyzed actual provider discussions with undecided parents to explore how parents express hesitancy about the HPV vaccine and how providers respond.”
Overall, 37 parents expressed hesitancy one or more times in different ways, including assertive responses (such as “No, not right now” or “We need to think about that”) at 27 visits, questions (such as “Is it safe?”) at 16 visits, and concerns (such as “I’m just nervous about it”) at 12 visits.
In responding to these parents, pediatricians used only persistence to promote vaccination in 18 cases, a combination of acquiescence and persistence in 13 cases, and only acquiescence in 6 cases. The teens were vaccinated the same day in 17 of the 18 cases of persistence, compared with only 2 of 13 cases of combined acquiescence and persistence, and none of the 6 cases in which health care providers acquiesced to parents’ concerns without further discussion.
The findings were limited by several factors, including a relatively homogeneous population of low socioeconomic families, too small a sample to determine significance, and possible influence of the audio recorder on behavior, Dr. Shay and her researchers noted. However, the results provide a framework for studies of parental hesitancy in larger and more diverse groups. “Parental hesitancy is an opportunity to practice patient-centered communication. Without understanding the source of parental hesitancy, a provider’s response may not be suitably tailored to counter hesitation”
“With our exploratory examination of the relationship between parent-provider communication about HPV vaccine hesitancy and vaccination behavior, we suggest that persistently engaging parents who express hesitancy can lead to same-day vaccinations and that these conversations are short (approximately 2-3 minutes),” they added.
The study was funded by the National Institutes of Health. Additional support was provided by the Simmons Comprehensive Cancer Center, University of Texas Southwestern Center for Translational Medicine, through the NIH and National Center for Advancing Translational Sciences, and University of Texas Southwestern Center of Patient-Centered Outcomes Research. Dr. Shay and her associates had no financial conflicts.
SOURCE: Shay LA et al. Pediatrics. 2018 May 15. doi: 10. 1542/ peds. 2017- 2312.
according to data from 43 pediatrician clinic visits at six clinics in Texas.
Vaccine hesitancy is on the rise among parents in the United States, wrote Laura A. Shay, PhD, of the University of Texas School of Public Health, San Antonio, and her colleagues. “Although vaccine hesitancy is subject to influence, to our knowledge, no authors of previous studies have analyzed actual provider discussions with undecided parents to explore how parents express hesitancy about the HPV vaccine and how providers respond.”
Overall, 37 parents expressed hesitancy one or more times in different ways, including assertive responses (such as “No, not right now” or “We need to think about that”) at 27 visits, questions (such as “Is it safe?”) at 16 visits, and concerns (such as “I’m just nervous about it”) at 12 visits.
In responding to these parents, pediatricians used only persistence to promote vaccination in 18 cases, a combination of acquiescence and persistence in 13 cases, and only acquiescence in 6 cases. The teens were vaccinated the same day in 17 of the 18 cases of persistence, compared with only 2 of 13 cases of combined acquiescence and persistence, and none of the 6 cases in which health care providers acquiesced to parents’ concerns without further discussion.
The findings were limited by several factors, including a relatively homogeneous population of low socioeconomic families, too small a sample to determine significance, and possible influence of the audio recorder on behavior, Dr. Shay and her researchers noted. However, the results provide a framework for studies of parental hesitancy in larger and more diverse groups. “Parental hesitancy is an opportunity to practice patient-centered communication. Without understanding the source of parental hesitancy, a provider’s response may not be suitably tailored to counter hesitation”
“With our exploratory examination of the relationship between parent-provider communication about HPV vaccine hesitancy and vaccination behavior, we suggest that persistently engaging parents who express hesitancy can lead to same-day vaccinations and that these conversations are short (approximately 2-3 minutes),” they added.
The study was funded by the National Institutes of Health. Additional support was provided by the Simmons Comprehensive Cancer Center, University of Texas Southwestern Center for Translational Medicine, through the NIH and National Center for Advancing Translational Sciences, and University of Texas Southwestern Center of Patient-Centered Outcomes Research. Dr. Shay and her associates had no financial conflicts.
SOURCE: Shay LA et al. Pediatrics. 2018 May 15. doi: 10. 1542/ peds. 2017- 2312.
according to data from 43 pediatrician clinic visits at six clinics in Texas.
Vaccine hesitancy is on the rise among parents in the United States, wrote Laura A. Shay, PhD, of the University of Texas School of Public Health, San Antonio, and her colleagues. “Although vaccine hesitancy is subject to influence, to our knowledge, no authors of previous studies have analyzed actual provider discussions with undecided parents to explore how parents express hesitancy about the HPV vaccine and how providers respond.”
Overall, 37 parents expressed hesitancy one or more times in different ways, including assertive responses (such as “No, not right now” or “We need to think about that”) at 27 visits, questions (such as “Is it safe?”) at 16 visits, and concerns (such as “I’m just nervous about it”) at 12 visits.
In responding to these parents, pediatricians used only persistence to promote vaccination in 18 cases, a combination of acquiescence and persistence in 13 cases, and only acquiescence in 6 cases. The teens were vaccinated the same day in 17 of the 18 cases of persistence, compared with only 2 of 13 cases of combined acquiescence and persistence, and none of the 6 cases in which health care providers acquiesced to parents’ concerns without further discussion.
The findings were limited by several factors, including a relatively homogeneous population of low socioeconomic families, too small a sample to determine significance, and possible influence of the audio recorder on behavior, Dr. Shay and her researchers noted. However, the results provide a framework for studies of parental hesitancy in larger and more diverse groups. “Parental hesitancy is an opportunity to practice patient-centered communication. Without understanding the source of parental hesitancy, a provider’s response may not be suitably tailored to counter hesitation”
“With our exploratory examination of the relationship between parent-provider communication about HPV vaccine hesitancy and vaccination behavior, we suggest that persistently engaging parents who express hesitancy can lead to same-day vaccinations and that these conversations are short (approximately 2-3 minutes),” they added.
The study was funded by the National Institutes of Health. Additional support was provided by the Simmons Comprehensive Cancer Center, University of Texas Southwestern Center for Translational Medicine, through the NIH and National Center for Advancing Translational Sciences, and University of Texas Southwestern Center of Patient-Centered Outcomes Research. Dr. Shay and her associates had no financial conflicts.
SOURCE: Shay LA et al. Pediatrics. 2018 May 15. doi: 10. 1542/ peds. 2017- 2312.
FROM PEDIATRICS
Key clinical point: A majority of unvaccinated adolescents received the HPV vaccine when clinicians engaged with hesitant parents.
Major finding: At 18 office visits when parents hesitated but doctors persisted, 17 adolescents received the HPV vaccine
Study details: The data come from audio recordings of 43 visits to six pediatric clinics in Dallas at which parents were unsure about HPV vaccination for their teens.
Disclosures: The study was funded by the National Institutes of Health. Additional support was provided by the Simmons Comprehensive Cancer Center, University of Texas Southwestern Center for Translational Medicine, through the NIH and National Center for Advancing Translational Sciences, and University of Texas Southwestern Center of Patient-Centered Outcomes Research. Dr. Shay and her associates had no financial conflicts.
Source: Shay LA et al. Pediatrics. 2018 May 15. doi: 10. 1542/ peds. 2017- 2312.
ADHD, asthma Rxs up
Use of prescription medication overall decreased in children and adolescents over the past 15 years, but certain medication classes saw increases over that time period, according to a comprehensive analysis of cross-sectional, nationally representative survey data.
Reported use of any prescription medication in the past 30 days decreased from 25% during 1999-2002 to 22% during 2011-2014 (P = .04), according to the analysis based on data from 38,277 children and adolescents aged 0-19 years in the National Health and Nutrition Examination Survey (NHANES).
However, the study showed increases over time in prescribing of medications for asthma, ADHD, and contraception, according to Craig M. Hales, MD, of the National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Md., and his coinvestigators.
“Monitoring trends in use of prescription medications among children and adolescents provides insights on several important public health concerns, such as shifting disease burden, changes in access to health care and medicines, increases in the adoption of appropriate therapies, and decreases in use of inappropriate or ineffective treatments,” Dr. Hales and his coauthors said.
They found significant linear trends in 14 therapeutic classes or subclasses, including six decreases and eight increases, when looking at combined survey data for reported use of any prescription medication and reported use of two or more prescription medications in the prior 30 days.
Of note, antibiotic usage decreased significantly from 8% during 1999-2002 to 5% during 2011-2014, including decreases in amoxicillin, amoxicillin/clavulanate, and cephalosporins. Likewise, antihistamine use was down over time, from 4% to 2%, as was use of upper respiratory combination medications, which decreased from 2% to 0.5%.
Conversely, they found prevalence of ADHD medication usage increased significantly from 3% during 1999-2002 to 4% during 2011-2014, including significant increases for both amphetamines and centrally acting adrenergic agents.
Asthma medication also increased, from 4% to 6%, including significant increases in inhaled corticosteroids and montelukast. Likewise, a significant increase in proton pump inhibitors was reported from 0.2% to 0.7%, while contraceptive use in girls increased significantly in prevalence, from 1% to 2%.
Taken together, these findings suggest an overall decrease in medication prescribing among children and adolescents, despite significantly increased prevalence of prescribing for certain drug classes, the investigators said.
They noted that the study had limitations. For example, NHANES does not include data on most over-the-counter medications, and for the drugs it does include, there are no data on dosages, frequency of use, or specific formulations, they said.
Dr. Hales and his coauthors had no conflicts of interest.
SOURCE: Hales CM et al. JAMA. 2018;319(19):2009-20.
These thorough analyses of medication prescribing for children and adolescents are much needed, but are “frustrating” because definitive conclusions cannot be drawn because of inherent limitations of the serial, cross-sectional study design, Gary L. Freed, MD, MPH, said in an editorial.
The study by Hales et al. shows an overall decrease in prescription medication use in children and adolescents based on data from the 1999-2014 National Health and Examination Survey (NHANES). The study shows increased use of medications for asthma, ADHD, and contraception, and decreased use of antibiotics, antihistamines, and upper respiratory combination medications.
“Some of these trends likely signal potential improvements in the care of children, others may suggest little progress has been made, and yet others are difficult to interpret with certainty,” Dr. Freed wrote.
One finding that seems clear in the data, according to Dr. Freed, is a decrease in antibiotic use among children and adolescents, from 8% to 5% from the 1999-2002 to 2011-2014 time period. That likely reflects the success of efforts to decrease overuse of these agents in community settings.
On the other hand, the decreased use of antihistamines documented in this study may reflect the success of efforts to reduce overuse, or the fact that several prescription medications became approved for OTC use over the course of the study. NHANES does not include OTC drug data in its survey.
“It is unclear whether there was simply a substitution effect and the actual overall rate of utilization of these medications was unchanged,” Dr. Freed wrote.
Increased amphetamine use for the treatment of children aged 6-11 years with ADHD is “vexing” to see, but again, caution must be exercised in interpreting the results, he said, because they do not clearly demonstrate whether these agents are being overused or underused.
“The findings reported by Hales et al. will require additional studies, using different data sources, to provide clarity in the clinical and policy implications of recent trends in medication use among children,” Dr. Freed wrote.
Dr. Freed is a pediatrician with the Child Health Evaluation and Research Center, University of Michigan, Ann Arbor. These comments are derived from his editorial accompanying the study by Hales et al. (JAMA. 2018;319[19]:1988-9). Dr. Freed had no conflicts of interest.
These thorough analyses of medication prescribing for children and adolescents are much needed, but are “frustrating” because definitive conclusions cannot be drawn because of inherent limitations of the serial, cross-sectional study design, Gary L. Freed, MD, MPH, said in an editorial.
The study by Hales et al. shows an overall decrease in prescription medication use in children and adolescents based on data from the 1999-2014 National Health and Examination Survey (NHANES). The study shows increased use of medications for asthma, ADHD, and contraception, and decreased use of antibiotics, antihistamines, and upper respiratory combination medications.
“Some of these trends likely signal potential improvements in the care of children, others may suggest little progress has been made, and yet others are difficult to interpret with certainty,” Dr. Freed wrote.
One finding that seems clear in the data, according to Dr. Freed, is a decrease in antibiotic use among children and adolescents, from 8% to 5% from the 1999-2002 to 2011-2014 time period. That likely reflects the success of efforts to decrease overuse of these agents in community settings.
On the other hand, the decreased use of antihistamines documented in this study may reflect the success of efforts to reduce overuse, or the fact that several prescription medications became approved for OTC use over the course of the study. NHANES does not include OTC drug data in its survey.
“It is unclear whether there was simply a substitution effect and the actual overall rate of utilization of these medications was unchanged,” Dr. Freed wrote.
Increased amphetamine use for the treatment of children aged 6-11 years with ADHD is “vexing” to see, but again, caution must be exercised in interpreting the results, he said, because they do not clearly demonstrate whether these agents are being overused or underused.
“The findings reported by Hales et al. will require additional studies, using different data sources, to provide clarity in the clinical and policy implications of recent trends in medication use among children,” Dr. Freed wrote.
Dr. Freed is a pediatrician with the Child Health Evaluation and Research Center, University of Michigan, Ann Arbor. These comments are derived from his editorial accompanying the study by Hales et al. (JAMA. 2018;319[19]:1988-9). Dr. Freed had no conflicts of interest.
These thorough analyses of medication prescribing for children and adolescents are much needed, but are “frustrating” because definitive conclusions cannot be drawn because of inherent limitations of the serial, cross-sectional study design, Gary L. Freed, MD, MPH, said in an editorial.
The study by Hales et al. shows an overall decrease in prescription medication use in children and adolescents based on data from the 1999-2014 National Health and Examination Survey (NHANES). The study shows increased use of medications for asthma, ADHD, and contraception, and decreased use of antibiotics, antihistamines, and upper respiratory combination medications.
“Some of these trends likely signal potential improvements in the care of children, others may suggest little progress has been made, and yet others are difficult to interpret with certainty,” Dr. Freed wrote.
One finding that seems clear in the data, according to Dr. Freed, is a decrease in antibiotic use among children and adolescents, from 8% to 5% from the 1999-2002 to 2011-2014 time period. That likely reflects the success of efforts to decrease overuse of these agents in community settings.
On the other hand, the decreased use of antihistamines documented in this study may reflect the success of efforts to reduce overuse, or the fact that several prescription medications became approved for OTC use over the course of the study. NHANES does not include OTC drug data in its survey.
“It is unclear whether there was simply a substitution effect and the actual overall rate of utilization of these medications was unchanged,” Dr. Freed wrote.
Increased amphetamine use for the treatment of children aged 6-11 years with ADHD is “vexing” to see, but again, caution must be exercised in interpreting the results, he said, because they do not clearly demonstrate whether these agents are being overused or underused.
“The findings reported by Hales et al. will require additional studies, using different data sources, to provide clarity in the clinical and policy implications of recent trends in medication use among children,” Dr. Freed wrote.
Dr. Freed is a pediatrician with the Child Health Evaluation and Research Center, University of Michigan, Ann Arbor. These comments are derived from his editorial accompanying the study by Hales et al. (JAMA. 2018;319[19]:1988-9). Dr. Freed had no conflicts of interest.
Use of prescription medication overall decreased in children and adolescents over the past 15 years, but certain medication classes saw increases over that time period, according to a comprehensive analysis of cross-sectional, nationally representative survey data.
Reported use of any prescription medication in the past 30 days decreased from 25% during 1999-2002 to 22% during 2011-2014 (P = .04), according to the analysis based on data from 38,277 children and adolescents aged 0-19 years in the National Health and Nutrition Examination Survey (NHANES).
However, the study showed increases over time in prescribing of medications for asthma, ADHD, and contraception, according to Craig M. Hales, MD, of the National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Md., and his coinvestigators.
“Monitoring trends in use of prescription medications among children and adolescents provides insights on several important public health concerns, such as shifting disease burden, changes in access to health care and medicines, increases in the adoption of appropriate therapies, and decreases in use of inappropriate or ineffective treatments,” Dr. Hales and his coauthors said.
They found significant linear trends in 14 therapeutic classes or subclasses, including six decreases and eight increases, when looking at combined survey data for reported use of any prescription medication and reported use of two or more prescription medications in the prior 30 days.
Of note, antibiotic usage decreased significantly from 8% during 1999-2002 to 5% during 2011-2014, including decreases in amoxicillin, amoxicillin/clavulanate, and cephalosporins. Likewise, antihistamine use was down over time, from 4% to 2%, as was use of upper respiratory combination medications, which decreased from 2% to 0.5%.
Conversely, they found prevalence of ADHD medication usage increased significantly from 3% during 1999-2002 to 4% during 2011-2014, including significant increases for both amphetamines and centrally acting adrenergic agents.
Asthma medication also increased, from 4% to 6%, including significant increases in inhaled corticosteroids and montelukast. Likewise, a significant increase in proton pump inhibitors was reported from 0.2% to 0.7%, while contraceptive use in girls increased significantly in prevalence, from 1% to 2%.
Taken together, these findings suggest an overall decrease in medication prescribing among children and adolescents, despite significantly increased prevalence of prescribing for certain drug classes, the investigators said.
They noted that the study had limitations. For example, NHANES does not include data on most over-the-counter medications, and for the drugs it does include, there are no data on dosages, frequency of use, or specific formulations, they said.
Dr. Hales and his coauthors had no conflicts of interest.
SOURCE: Hales CM et al. JAMA. 2018;319(19):2009-20.
Use of prescription medication overall decreased in children and adolescents over the past 15 years, but certain medication classes saw increases over that time period, according to a comprehensive analysis of cross-sectional, nationally representative survey data.
Reported use of any prescription medication in the past 30 days decreased from 25% during 1999-2002 to 22% during 2011-2014 (P = .04), according to the analysis based on data from 38,277 children and adolescents aged 0-19 years in the National Health and Nutrition Examination Survey (NHANES).
However, the study showed increases over time in prescribing of medications for asthma, ADHD, and contraception, according to Craig M. Hales, MD, of the National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Md., and his coinvestigators.
“Monitoring trends in use of prescription medications among children and adolescents provides insights on several important public health concerns, such as shifting disease burden, changes in access to health care and medicines, increases in the adoption of appropriate therapies, and decreases in use of inappropriate or ineffective treatments,” Dr. Hales and his coauthors said.
They found significant linear trends in 14 therapeutic classes or subclasses, including six decreases and eight increases, when looking at combined survey data for reported use of any prescription medication and reported use of two or more prescription medications in the prior 30 days.
Of note, antibiotic usage decreased significantly from 8% during 1999-2002 to 5% during 2011-2014, including decreases in amoxicillin, amoxicillin/clavulanate, and cephalosporins. Likewise, antihistamine use was down over time, from 4% to 2%, as was use of upper respiratory combination medications, which decreased from 2% to 0.5%.
Conversely, they found prevalence of ADHD medication usage increased significantly from 3% during 1999-2002 to 4% during 2011-2014, including significant increases for both amphetamines and centrally acting adrenergic agents.
Asthma medication also increased, from 4% to 6%, including significant increases in inhaled corticosteroids and montelukast. Likewise, a significant increase in proton pump inhibitors was reported from 0.2% to 0.7%, while contraceptive use in girls increased significantly in prevalence, from 1% to 2%.
Taken together, these findings suggest an overall decrease in medication prescribing among children and adolescents, despite significantly increased prevalence of prescribing for certain drug classes, the investigators said.
They noted that the study had limitations. For example, NHANES does not include data on most over-the-counter medications, and for the drugs it does include, there are no data on dosages, frequency of use, or specific formulations, they said.
Dr. Hales and his coauthors had no conflicts of interest.
SOURCE: Hales CM et al. JAMA. 2018;319(19):2009-20.
FROM JAMA
Key clinical point: Nationally representative survey data demonstrate an overall decrease in use of any medication among children and adolescents, although use of certain medications increased.
Major finding: (P = 0.04).
Study details: Analysis of survey data for U.S. children and adolescents aged 0-19 years in the 1999-2014 NHANES.
Disclosures: Dr. Hales and his coauthors had no conflicts of interest.
Source: Hales CM et al. JAMA. 2018;319(19):2009-20.
Treating Migraines: It’s Different for Kids
A 15-year-old girl presents to your clinic with poorly controlled chronic migraines that prevent her from attending school three to four days per month. As part of her treatment regimen, you are considering migraine prevention strategies. Should you prescribe amitriptyline or topiramate?
Migraine headaches are the most common reason for headache presentation in pediatric neurology outpatient clinics, affecting 5% to 10% of the pediatric population worldwide.2 Current recommendations regarding prophylactic migraine therapy in childhood are based on consensus opinions.3,4 While the FDA has not approved any medications for migraine prevention in children younger than 12, surveys of pediatric headache specialists suggest that amitriptyline and topiramate are among the most commonly prescribed medications for childhood migraine prophylaxis.3,4
There is low-quality evidence from individual RCTs about the effectiveness of topiramate. A meta-analysis by El-Chammas and colleagues included three RCTs comparing topiramate to placebo for the prevention of episodic migraines (migraine headaches that occur < 15 x/mo) in a combined total of 283 children younger than 18.5 Topiramate demonstrated a nonclinically significant, but statistically significant, reduction of less than one headache per month (–0.71). This is based on moderate-quality evidence due to a high placebo response rate and study durations of only 12 weeks.5 The FDA has approved topiramate for migraine prevention in children ages 12 to 17.6
Adult guidelines. The findings described above are consistent with the most recent adult guidelines from the American Academy of Neurology and the American Headache Society.7 In a joint publication from 2012, these societies recommended both topiramate and amitriptyline for the prevention of migraines in adults based on high-quality (Level A) and medium-quality (Level B) evidence, respectively.7
STUDY SUMMARY
No better than placebo in children
A multicenter, double-blind RCT by Powers and colleagues compared the effectiveness of amitriptyline, topiramate, and placebo in the prevention of pediatric migraines.1 Target dosing for amitriptyline and topiramate was set at 1 mg/kg/d and 2 mg/kg/d, respectively. Titration toward these doses occurred over an eight-week period, based on reported adverse effects. Patients then continued their maximum tolerated dose for an additional 16 weeks.
Patients were predominantly white (70%), female (68%), and 8 to 17 years of age. They had at least four headache days over a prospective 28-day pretreatment period and a Pediatric Migraine Disability Assessment Scale (PedMIDAS) score of 11 to 139 (scores of 11-50 indicate mild-to-moderate disability; of > 50, severe disability).1,8 The primary endpoint consisted of at least a 50% relative reduction (RR) in the number of headache days in the final 28 days of the trial, compared to the 28-day pretherapy (baseline) period.1
The authors of the study included 328 patients in the primary efficacy analysis and randomly assigned them in a 2:2:1 ratio to receive either amitriptyline (132 patients), topiramate (130 patients), or placebo (66 patients). After 24 weeks of therapy, there was no significant difference between the amitriptyline, topiramate, and placebo groups in the primary endpoint (52% amitriptyline, 55% topiramate, 61% placebo; adjusted odds ratio [OR], 0.71 between amitriptyline and placebo; OR, 0.81 between topiramate and placebo; OR, 0.88 between amitriptyline and topiramate).
Continue to: There was also no difference...
There was also no difference in the secondary outcomes of absolute reduction in headache days and headache-related disability as determined by PedMIDAS. The study was stopped early for futility. Compared with placebo, amitriptyline significantly increased fatigue (number needed to harm [NNH], 8) and dry mouth (NNH, 9) and was associated with three serious adverse events of altered mood. Compared with placebo, topiramate significantly increased paresthesia (NNH, 4) and weight loss (NNH, 13) and was associated with one serious adverse event—a suicide attempt.1
WHAT’S NEW?
Higher-level evidence, lack of efficacy
This RCT provides new, higher-level evidence that demonstrates the lack of efficacy of amitriptyline and topiramate in the prevention of pediatric migraines. It also highlights the risk for increased adverse events with topiramate and amitriptyline.
Two of the three topiramate trials used in the older meta-analysis by El-Chammas and colleagues and this new RCT were included in an updated meta-analysis by Le and colleagues (total participants, 465) published in 2017.1,2,5 This newer meta-analysis found no statistical benefit associated with the use of topiramate over placebo. It demonstrated a nonsignificant decrease in the number of patients with at least a 50% relative reduction in headache frequency (risk ratio, 1.26) and in the overall number of headache days (mean difference, –0.77) in patients younger than 18.2 Both meta-analyses, however, showed an increase in the rate of adverse events in patients using topiramate versus placebo.2,5
CAVEATS
Is there a gender predominance?
El-Chammas and colleagues describe male pediatric patients as being the predominant pediatric gender with migraines.5 However, they do not quote an incidence rate or cite the reference for this statement. No other reference to gender predominance was noted in the literature. The current study, in addition to the total population of the meta-analysis by Le and colleagues, included women as the predominant patient population.1,2 Hopefully, future studies will help to delineate whether there is a gender predominance and, if so, whether the current treatment data apply to both genders.
Continue to: CHALLENGES TO IMPLEMENTATION
CHALLENGES TO IMPLEMENTATION
None to speak of
There are no barriers to implementing this recommendation immediately.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018;67 [4]:238-239, 241).
1. Powers SW, Coffey CS, Chamberlin LA, et al; for the CHAMP Investigators. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2017; 376:115-124.
2. Le K, Yu D, Wang J, et al. Is topiramate effective for migraine prevention in patients less than 18 years of age? A meta-analysis of randomized controlled trials. J Headache Pain. 2017;18:69.
3. Lewis D, Ashwal S, Hershey A, et al. Practice parameter: pharmacological treatment of migraine headache in children and adolescents: report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of the Child Neurology Society. Neurology. 2004;63:2215-2224.
4. Hershey AD. Current approaches to the diagnosis and management of paediatric migraine. Lancet Neurology. 2010;9:190-204.
5. El-Chammas K, Keyes J, Thompson N, et al. Pharmacologic treatment of pediatric headaches: a meta-analysis. JAMA Pediatr. 2013;167:250-258.
6. Qudexy XR. Highlights of prescribing information. www.accessdata.fda.gov/drugsatfda_docs/label/2017/205122s003s005lbl.pdf. Accessed April 6, 2018.
7. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78:1337-1345.
8. Hershey AD, Powers SW, Vockell AL, et al. PedMIDAS: development of a questionnaire to assess disability of migraines in children. Neurology. 2001;57:2034-2039.
A 15-year-old girl presents to your clinic with poorly controlled chronic migraines that prevent her from attending school three to four days per month. As part of her treatment regimen, you are considering migraine prevention strategies. Should you prescribe amitriptyline or topiramate?
Migraine headaches are the most common reason for headache presentation in pediatric neurology outpatient clinics, affecting 5% to 10% of the pediatric population worldwide.2 Current recommendations regarding prophylactic migraine therapy in childhood are based on consensus opinions.3,4 While the FDA has not approved any medications for migraine prevention in children younger than 12, surveys of pediatric headache specialists suggest that amitriptyline and topiramate are among the most commonly prescribed medications for childhood migraine prophylaxis.3,4
There is low-quality evidence from individual RCTs about the effectiveness of topiramate. A meta-analysis by El-Chammas and colleagues included three RCTs comparing topiramate to placebo for the prevention of episodic migraines (migraine headaches that occur < 15 x/mo) in a combined total of 283 children younger than 18.5 Topiramate demonstrated a nonclinically significant, but statistically significant, reduction of less than one headache per month (–0.71). This is based on moderate-quality evidence due to a high placebo response rate and study durations of only 12 weeks.5 The FDA has approved topiramate for migraine prevention in children ages 12 to 17.6
Adult guidelines. The findings described above are consistent with the most recent adult guidelines from the American Academy of Neurology and the American Headache Society.7 In a joint publication from 2012, these societies recommended both topiramate and amitriptyline for the prevention of migraines in adults based on high-quality (Level A) and medium-quality (Level B) evidence, respectively.7
STUDY SUMMARY
No better than placebo in children
A multicenter, double-blind RCT by Powers and colleagues compared the effectiveness of amitriptyline, topiramate, and placebo in the prevention of pediatric migraines.1 Target dosing for amitriptyline and topiramate was set at 1 mg/kg/d and 2 mg/kg/d, respectively. Titration toward these doses occurred over an eight-week period, based on reported adverse effects. Patients then continued their maximum tolerated dose for an additional 16 weeks.
Patients were predominantly white (70%), female (68%), and 8 to 17 years of age. They had at least four headache days over a prospective 28-day pretreatment period and a Pediatric Migraine Disability Assessment Scale (PedMIDAS) score of 11 to 139 (scores of 11-50 indicate mild-to-moderate disability; of > 50, severe disability).1,8 The primary endpoint consisted of at least a 50% relative reduction (RR) in the number of headache days in the final 28 days of the trial, compared to the 28-day pretherapy (baseline) period.1
The authors of the study included 328 patients in the primary efficacy analysis and randomly assigned them in a 2:2:1 ratio to receive either amitriptyline (132 patients), topiramate (130 patients), or placebo (66 patients). After 24 weeks of therapy, there was no significant difference between the amitriptyline, topiramate, and placebo groups in the primary endpoint (52% amitriptyline, 55% topiramate, 61% placebo; adjusted odds ratio [OR], 0.71 between amitriptyline and placebo; OR, 0.81 between topiramate and placebo; OR, 0.88 between amitriptyline and topiramate).
Continue to: There was also no difference...
There was also no difference in the secondary outcomes of absolute reduction in headache days and headache-related disability as determined by PedMIDAS. The study was stopped early for futility. Compared with placebo, amitriptyline significantly increased fatigue (number needed to harm [NNH], 8) and dry mouth (NNH, 9) and was associated with three serious adverse events of altered mood. Compared with placebo, topiramate significantly increased paresthesia (NNH, 4) and weight loss (NNH, 13) and was associated with one serious adverse event—a suicide attempt.1
WHAT’S NEW?
Higher-level evidence, lack of efficacy
This RCT provides new, higher-level evidence that demonstrates the lack of efficacy of amitriptyline and topiramate in the prevention of pediatric migraines. It also highlights the risk for increased adverse events with topiramate and amitriptyline.
Two of the three topiramate trials used in the older meta-analysis by El-Chammas and colleagues and this new RCT were included in an updated meta-analysis by Le and colleagues (total participants, 465) published in 2017.1,2,5 This newer meta-analysis found no statistical benefit associated with the use of topiramate over placebo. It demonstrated a nonsignificant decrease in the number of patients with at least a 50% relative reduction in headache frequency (risk ratio, 1.26) and in the overall number of headache days (mean difference, –0.77) in patients younger than 18.2 Both meta-analyses, however, showed an increase in the rate of adverse events in patients using topiramate versus placebo.2,5
CAVEATS
Is there a gender predominance?
El-Chammas and colleagues describe male pediatric patients as being the predominant pediatric gender with migraines.5 However, they do not quote an incidence rate or cite the reference for this statement. No other reference to gender predominance was noted in the literature. The current study, in addition to the total population of the meta-analysis by Le and colleagues, included women as the predominant patient population.1,2 Hopefully, future studies will help to delineate whether there is a gender predominance and, if so, whether the current treatment data apply to both genders.
Continue to: CHALLENGES TO IMPLEMENTATION
CHALLENGES TO IMPLEMENTATION
None to speak of
There are no barriers to implementing this recommendation immediately.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018;67 [4]:238-239, 241).
A 15-year-old girl presents to your clinic with poorly controlled chronic migraines that prevent her from attending school three to four days per month. As part of her treatment regimen, you are considering migraine prevention strategies. Should you prescribe amitriptyline or topiramate?
Migraine headaches are the most common reason for headache presentation in pediatric neurology outpatient clinics, affecting 5% to 10% of the pediatric population worldwide.2 Current recommendations regarding prophylactic migraine therapy in childhood are based on consensus opinions.3,4 While the FDA has not approved any medications for migraine prevention in children younger than 12, surveys of pediatric headache specialists suggest that amitriptyline and topiramate are among the most commonly prescribed medications for childhood migraine prophylaxis.3,4
There is low-quality evidence from individual RCTs about the effectiveness of topiramate. A meta-analysis by El-Chammas and colleagues included three RCTs comparing topiramate to placebo for the prevention of episodic migraines (migraine headaches that occur < 15 x/mo) in a combined total of 283 children younger than 18.5 Topiramate demonstrated a nonclinically significant, but statistically significant, reduction of less than one headache per month (–0.71). This is based on moderate-quality evidence due to a high placebo response rate and study durations of only 12 weeks.5 The FDA has approved topiramate for migraine prevention in children ages 12 to 17.6
Adult guidelines. The findings described above are consistent with the most recent adult guidelines from the American Academy of Neurology and the American Headache Society.7 In a joint publication from 2012, these societies recommended both topiramate and amitriptyline for the prevention of migraines in adults based on high-quality (Level A) and medium-quality (Level B) evidence, respectively.7
STUDY SUMMARY
No better than placebo in children
A multicenter, double-blind RCT by Powers and colleagues compared the effectiveness of amitriptyline, topiramate, and placebo in the prevention of pediatric migraines.1 Target dosing for amitriptyline and topiramate was set at 1 mg/kg/d and 2 mg/kg/d, respectively. Titration toward these doses occurred over an eight-week period, based on reported adverse effects. Patients then continued their maximum tolerated dose for an additional 16 weeks.
Patients were predominantly white (70%), female (68%), and 8 to 17 years of age. They had at least four headache days over a prospective 28-day pretreatment period and a Pediatric Migraine Disability Assessment Scale (PedMIDAS) score of 11 to 139 (scores of 11-50 indicate mild-to-moderate disability; of > 50, severe disability).1,8 The primary endpoint consisted of at least a 50% relative reduction (RR) in the number of headache days in the final 28 days of the trial, compared to the 28-day pretherapy (baseline) period.1
The authors of the study included 328 patients in the primary efficacy analysis and randomly assigned them in a 2:2:1 ratio to receive either amitriptyline (132 patients), topiramate (130 patients), or placebo (66 patients). After 24 weeks of therapy, there was no significant difference between the amitriptyline, topiramate, and placebo groups in the primary endpoint (52% amitriptyline, 55% topiramate, 61% placebo; adjusted odds ratio [OR], 0.71 between amitriptyline and placebo; OR, 0.81 between topiramate and placebo; OR, 0.88 between amitriptyline and topiramate).
Continue to: There was also no difference...
There was also no difference in the secondary outcomes of absolute reduction in headache days and headache-related disability as determined by PedMIDAS. The study was stopped early for futility. Compared with placebo, amitriptyline significantly increased fatigue (number needed to harm [NNH], 8) and dry mouth (NNH, 9) and was associated with three serious adverse events of altered mood. Compared with placebo, topiramate significantly increased paresthesia (NNH, 4) and weight loss (NNH, 13) and was associated with one serious adverse event—a suicide attempt.1
WHAT’S NEW?
Higher-level evidence, lack of efficacy
This RCT provides new, higher-level evidence that demonstrates the lack of efficacy of amitriptyline and topiramate in the prevention of pediatric migraines. It also highlights the risk for increased adverse events with topiramate and amitriptyline.
Two of the three topiramate trials used in the older meta-analysis by El-Chammas and colleagues and this new RCT were included in an updated meta-analysis by Le and colleagues (total participants, 465) published in 2017.1,2,5 This newer meta-analysis found no statistical benefit associated with the use of topiramate over placebo. It demonstrated a nonsignificant decrease in the number of patients with at least a 50% relative reduction in headache frequency (risk ratio, 1.26) and in the overall number of headache days (mean difference, –0.77) in patients younger than 18.2 Both meta-analyses, however, showed an increase in the rate of adverse events in patients using topiramate versus placebo.2,5
CAVEATS
Is there a gender predominance?
El-Chammas and colleagues describe male pediatric patients as being the predominant pediatric gender with migraines.5 However, they do not quote an incidence rate or cite the reference for this statement. No other reference to gender predominance was noted in the literature. The current study, in addition to the total population of the meta-analysis by Le and colleagues, included women as the predominant patient population.1,2 Hopefully, future studies will help to delineate whether there is a gender predominance and, if so, whether the current treatment data apply to both genders.
Continue to: CHALLENGES TO IMPLEMENTATION
CHALLENGES TO IMPLEMENTATION
None to speak of
There are no barriers to implementing this recommendation immediately.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.
Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018;67 [4]:238-239, 241).
1. Powers SW, Coffey CS, Chamberlin LA, et al; for the CHAMP Investigators. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2017; 376:115-124.
2. Le K, Yu D, Wang J, et al. Is topiramate effective for migraine prevention in patients less than 18 years of age? A meta-analysis of randomized controlled trials. J Headache Pain. 2017;18:69.
3. Lewis D, Ashwal S, Hershey A, et al. Practice parameter: pharmacological treatment of migraine headache in children and adolescents: report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of the Child Neurology Society. Neurology. 2004;63:2215-2224.
4. Hershey AD. Current approaches to the diagnosis and management of paediatric migraine. Lancet Neurology. 2010;9:190-204.
5. El-Chammas K, Keyes J, Thompson N, et al. Pharmacologic treatment of pediatric headaches: a meta-analysis. JAMA Pediatr. 2013;167:250-258.
6. Qudexy XR. Highlights of prescribing information. www.accessdata.fda.gov/drugsatfda_docs/label/2017/205122s003s005lbl.pdf. Accessed April 6, 2018.
7. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78:1337-1345.
8. Hershey AD, Powers SW, Vockell AL, et al. PedMIDAS: development of a questionnaire to assess disability of migraines in children. Neurology. 2001;57:2034-2039.
1. Powers SW, Coffey CS, Chamberlin LA, et al; for the CHAMP Investigators. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2017; 376:115-124.
2. Le K, Yu D, Wang J, et al. Is topiramate effective for migraine prevention in patients less than 18 years of age? A meta-analysis of randomized controlled trials. J Headache Pain. 2017;18:69.
3. Lewis D, Ashwal S, Hershey A, et al. Practice parameter: pharmacological treatment of migraine headache in children and adolescents: report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of the Child Neurology Society. Neurology. 2004;63:2215-2224.
4. Hershey AD. Current approaches to the diagnosis and management of paediatric migraine. Lancet Neurology. 2010;9:190-204.
5. El-Chammas K, Keyes J, Thompson N, et al. Pharmacologic treatment of pediatric headaches: a meta-analysis. JAMA Pediatr. 2013;167:250-258.
6. Qudexy XR. Highlights of prescribing information. www.accessdata.fda.gov/drugsatfda_docs/label/2017/205122s003s005lbl.pdf. Accessed April 6, 2018.
7. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78:1337-1345.
8. Hershey AD, Powers SW, Vockell AL, et al. PedMIDAS: development of a questionnaire to assess disability of migraines in children. Neurology. 2001;57:2034-2039.
