Pediatrics

TORONTO – The majority of transgender youth attending a pediatric gender clinic were not willing to delay starting hormone therapy in order to pursue fertility preservation, according to a survey study presented during a poster session at the Pediatric Academic Societies annual meeting.

Five percent of 66 young people and 33% of 52 parents surveyed during a visit to a hospital-based gender clinic agreed with the statement: “I would choose to delay hormone therapy to undergo fertility preservation (for my child) if asked today.”

Further, 70% of youth agreed that discomfort with a part of the body they don’t identify with was a factor that influenced their decision or thoughts about fertility preservation. Religious, financial, ethical, and demographic factors were not associated with willingness to delay treatment for fertility concerns.

“While hormone therapy has drastically improved the lives of countless transgender and gender nonconforming youth, its impact on fertility can unfairly force individuals to decide at a very early age whether or not they should preserve the ability to be a biological parent one day,” Rebecca Persky, MD, said in a press release. Dr. Persky, a former Children’s Hospital of Philadelphia (CHOP) resident, is now is a pediatric endocrinology fellow at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

A slightly greater proportion of youth (20%) and 12% of parents agreed it was important to have biological children or grandchildren. For those youth who did want to preserve the option of having biological children, that desire was associated with perceiving it as important to their parents (odds ratio, 6.07; P less than .05).

“We didn’t ask any questions about adoption of children or grandchildren, so that might have yielded different results if we had,” Dr. Persky acknowledged in an interview.

A lack of information about whether hormone therapy definitely prevents biologic fertility was associated with parents’ willingness to delay treatment for fertility preservation (OR: 24.57, P less than .05), yet 62% of parents said they felt their children were able to “make a meaningful decision about taking steps to preserve fertility at this point in (his/her/their) life.”

“I thought delaying treatment would be one of the biggest barriers, but even when we asked them if they wanted to preserve their fertility while not delaying or changing their hormone therapy, only the minority [33%] said they would be interested in that,” Dr. Persky said in an interview. “It kind of argues that a lot of these kids just don’t want to have biological children.”

She noted, however, that one limitation of the study was that many of the children surveyed already were receiving hormone therapy such that the questions engaged more on a theoretical level than a practical one.

“Not surprisingly, the strongest factor in the parents’ decisions was whether or not it was important to their child to have biological children,” said Dr. Persky.

The researchers surveyed 66 transgender and gender nonconforming youth who presented for care at the Gender and Sexuality Development Clinic at CHOP. After the findings were released, it was noted by several concerned parties on Twitter that because of the location of the study, the sample was a decidedly selected one.

The mean age was 17 years of patients and 63% of the sample were assigned female sex at birth. The mean age in the 52 parents surveyed was 48 years. The survey included 36 items on knowledge of fertility preservation, the desire to have biological children, and other factors that may affect the decision to pursue fertility preservation.

Gender-specific and age-specific analyses have not been completed, but are in the works, said Dr. Persky, who acknowledged that the area requires more qualitative research.

The authors reported no conflicts of interest.

TORONTO – The majority of transgender youth attending a pediatric gender clinic were not willing to delay starting hormone therapy in order to pursue fertility preservation, according to a survey study presented during a poster session at the Pediatric Academic Societies annual meeting.

Five percent of 66 young people and 33% of 52 parents surveyed during a visit to a hospital-based gender clinic agreed with the statement: “I would choose to delay hormone therapy to undergo fertility preservation (for my child) if asked today.”

Further, 70% of youth agreed that discomfort with a part of the body they don’t identify with was a factor that influenced their decision or thoughts about fertility preservation. Religious, financial, ethical, and demographic factors were not associated with willingness to delay treatment for fertility concerns.

“While hormone therapy has drastically improved the lives of countless transgender and gender nonconforming youth, its impact on fertility can unfairly force individuals to decide at a very early age whether or not they should preserve the ability to be a biological parent one day,” Rebecca Persky, MD, said in a press release. Dr. Persky, a former Children’s Hospital of Philadelphia (CHOP) resident, is now is a pediatric endocrinology fellow at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

A slightly greater proportion of youth (20%) and 12% of parents agreed it was important to have biological children or grandchildren. For those youth who did want to preserve the option of having biological children, that desire was associated with perceiving it as important to their parents (odds ratio, 6.07; P less than .05).

“We didn’t ask any questions about adoption of children or grandchildren, so that might have yielded different results if we had,” Dr. Persky acknowledged in an interview.

A lack of information about whether hormone therapy definitely prevents biologic fertility was associated with parents’ willingness to delay treatment for fertility preservation (OR: 24.57, P less than .05), yet 62% of parents said they felt their children were able to “make a meaningful decision about taking steps to preserve fertility at this point in (his/her/their) life.”

“I thought delaying treatment would be one of the biggest barriers, but even when we asked them if they wanted to preserve their fertility while not delaying or changing their hormone therapy, only the minority [33%] said they would be interested in that,” Dr. Persky said in an interview. “It kind of argues that a lot of these kids just don’t want to have biological children.”

She noted, however, that one limitation of the study was that many of the children surveyed already were receiving hormone therapy such that the questions engaged more on a theoretical level than a practical one.

“Not surprisingly, the strongest factor in the parents’ decisions was whether or not it was important to their child to have biological children,” said Dr. Persky.

The researchers surveyed 66 transgender and gender nonconforming youth who presented for care at the Gender and Sexuality Development Clinic at CHOP. After the findings were released, it was noted by several concerned parties on Twitter that because of the location of the study, the sample was a decidedly selected one.

The mean age was 17 years of patients and 63% of the sample were assigned female sex at birth. The mean age in the 52 parents surveyed was 48 years. The survey included 36 items on knowledge of fertility preservation, the desire to have biological children, and other factors that may affect the decision to pursue fertility preservation.

Gender-specific and age-specific analyses have not been completed, but are in the works, said Dr. Persky, who acknowledged that the area requires more qualitative research.

The authors reported no conflicts of interest.

TORONTO – The majority of transgender youth attending a pediatric gender clinic were not willing to delay starting hormone therapy in order to pursue fertility preservation, according to a survey study presented during a poster session at the Pediatric Academic Societies annual meeting.

Five percent of 66 young people and 33% of 52 parents surveyed during a visit to a hospital-based gender clinic agreed with the statement: “I would choose to delay hormone therapy to undergo fertility preservation (for my child) if asked today.”

Further, 70% of youth agreed that discomfort with a part of the body they don’t identify with was a factor that influenced their decision or thoughts about fertility preservation. Religious, financial, ethical, and demographic factors were not associated with willingness to delay treatment for fertility concerns.

“While hormone therapy has drastically improved the lives of countless transgender and gender nonconforming youth, its impact on fertility can unfairly force individuals to decide at a very early age whether or not they should preserve the ability to be a biological parent one day,” Rebecca Persky, MD, said in a press release. Dr. Persky, a former Children’s Hospital of Philadelphia (CHOP) resident, is now is a pediatric endocrinology fellow at the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

A slightly greater proportion of youth (20%) and 12% of parents agreed it was important to have biological children or grandchildren. For those youth who did want to preserve the option of having biological children, that desire was associated with perceiving it as important to their parents (odds ratio, 6.07; P less than .05).

“We didn’t ask any questions about adoption of children or grandchildren, so that might have yielded different results if we had,” Dr. Persky acknowledged in an interview.

A lack of information about whether hormone therapy definitely prevents biologic fertility was associated with parents’ willingness to delay treatment for fertility preservation (OR: 24.57, P less than .05), yet 62% of parents said they felt their children were able to “make a meaningful decision about taking steps to preserve fertility at this point in (his/her/their) life.”

“I thought delaying treatment would be one of the biggest barriers, but even when we asked them if they wanted to preserve their fertility while not delaying or changing their hormone therapy, only the minority [33%] said they would be interested in that,” Dr. Persky said in an interview. “It kind of argues that a lot of these kids just don’t want to have biological children.”

She noted, however, that one limitation of the study was that many of the children surveyed already were receiving hormone therapy such that the questions engaged more on a theoretical level than a practical one.

“Not surprisingly, the strongest factor in the parents’ decisions was whether or not it was important to their child to have biological children,” said Dr. Persky.

The researchers surveyed 66 transgender and gender nonconforming youth who presented for care at the Gender and Sexuality Development Clinic at CHOP. After the findings were released, it was noted by several concerned parties on Twitter that because of the location of the study, the sample was a decidedly selected one.

The mean age was 17 years of patients and 63% of the sample were assigned female sex at birth. The mean age in the 52 parents surveyed was 48 years. The survey included 36 items on knowledge of fertility preservation, the desire to have biological children, and other factors that may affect the decision to pursue fertility preservation.

Gender-specific and age-specific analyses have not been completed, but are in the works, said Dr. Persky, who acknowledged that the area requires more qualitative research.

The authors reported no conflicts of interest.

Sleep has begun to emerge from the shadows to gain its rightful place in the health pantheon. With this emergence has come a motley group of physicians and self-proclaimed experts (myself included) eager to share their anecdotal evidence and opinions on how new parents can shorten the inevitable and often painfully slow process of settling in.

a-fitz/Stockphoto

A study in the May 2018 Journal of Pediatrics is an attempt to provide some data-driven guidance for sleep-deprived parents and their physician-advisors (“Real-World Implementation of Infant Behavioral Sleep Interventions: Results of a Parental Survey”). Using the responses from 652 parents who participated in a Facebook peer support group, the investigators created four categories of behavior sleep intervention for the parents of infants a mean age of 6 months: Modified extinction in which parents left the room and returned to briefly reassure the infant at intervals ranging from 5 to 25 minutes; unmodified extinction in which the parents let the infant cry it out; parental presence with support in which the parents remained in the room and interacted with the child; and parental presence without support. Extinction, both modified and unmodified (50% and 35%), was far and away the most frequently used method.

There was little difference in the effectiveness of the four strategies. By 2 weeks, 79% of the parents reported success, and the interventions were successfully discontinued in a mean and mode of 7 days. Not surprisingly, with success came reduced parental stress, as well as more consistent bedtime routines and smoother transitions to sleep.

When choosing a behavioral sleep intervention to suggest, I have tried to consider what I have learned about each family’s personality in the few months I have gotten to know them. But I have always been a big fan of extinction. And I suspect that my bias is simply a reflection of my no-nonsense, let’s-get-it-done-now personality. The results of this new study suggests that my poorly disguised pessimism about parental presence strategies may have discouraged some parents from trying an intervention that might have been successful for them.

The good news is that all four strategies can be successful. The problem is helping parents find the time and energy required to make any intervention successful. In the short term, extinction or parental presence is likely to mean less sleep for the parents. If work schedules and other family stressors already have drained a family’s energy reserves, it may not be the right time to try an intervention. When it becomes clear that there is never going to be right time, it is time for a frank discussion with the family about rearranging their priorities.

Behavioral sleep interventions require consistency and a family must be prepared to commit at least a week of uninterrupted evenings to get the job done. Business trips, visitors, and social engagements must take a back seat.

Extinction strategies are going to involve some crying, and while as pediatricians, we have developed the ability to buffer ourselves from crying (ignore really isn’t the right word), we must accept that listening to one’s child is too painful for some parents. When only one parent can’t tolerate the crying, the solution may be having that parent leave the home on the intervention evenings. When both parents share the vulnerability, the better answer is a parental presence strategy.

Although this study was small with a self-selected group of parents, the good news is that behavioral sleep intervention can work. We need to share the news with young families and encourage them to just do it.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Is My Child Overtired?: The Sleep Solution for Raising Happier, Healthier Children.” Email him at pdnews@mdedge.com.

Sleep has begun to emerge from the shadows to gain its rightful place in the health pantheon. With this emergence has come a motley group of physicians and self-proclaimed experts (myself included) eager to share their anecdotal evidence and opinions on how new parents can shorten the inevitable and often painfully slow process of settling in.

a-fitz/Stockphoto

A study in the May 2018 Journal of Pediatrics is an attempt to provide some data-driven guidance for sleep-deprived parents and their physician-advisors (“Real-World Implementation of Infant Behavioral Sleep Interventions: Results of a Parental Survey”). Using the responses from 652 parents who participated in a Facebook peer support group, the investigators created four categories of behavior sleep intervention for the parents of infants a mean age of 6 months: Modified extinction in which parents left the room and returned to briefly reassure the infant at intervals ranging from 5 to 25 minutes; unmodified extinction in which the parents let the infant cry it out; parental presence with support in which the parents remained in the room and interacted with the child; and parental presence without support. Extinction, both modified and unmodified (50% and 35%), was far and away the most frequently used method.

There was little difference in the effectiveness of the four strategies. By 2 weeks, 79% of the parents reported success, and the interventions were successfully discontinued in a mean and mode of 7 days. Not surprisingly, with success came reduced parental stress, as well as more consistent bedtime routines and smoother transitions to sleep.

When choosing a behavioral sleep intervention to suggest, I have tried to consider what I have learned about each family’s personality in the few months I have gotten to know them. But I have always been a big fan of extinction. And I suspect that my bias is simply a reflection of my no-nonsense, let’s-get-it-done-now personality. The results of this new study suggests that my poorly disguised pessimism about parental presence strategies may have discouraged some parents from trying an intervention that might have been successful for them.

The good news is that all four strategies can be successful. The problem is helping parents find the time and energy required to make any intervention successful. In the short term, extinction or parental presence is likely to mean less sleep for the parents. If work schedules and other family stressors already have drained a family’s energy reserves, it may not be the right time to try an intervention. When it becomes clear that there is never going to be right time, it is time for a frank discussion with the family about rearranging their priorities.

Behavioral sleep interventions require consistency and a family must be prepared to commit at least a week of uninterrupted evenings to get the job done. Business trips, visitors, and social engagements must take a back seat.

Extinction strategies are going to involve some crying, and while as pediatricians, we have developed the ability to buffer ourselves from crying (ignore really isn’t the right word), we must accept that listening to one’s child is too painful for some parents. When only one parent can’t tolerate the crying, the solution may be having that parent leave the home on the intervention evenings. When both parents share the vulnerability, the better answer is a parental presence strategy.

Although this study was small with a self-selected group of parents, the good news is that behavioral sleep intervention can work. We need to share the news with young families and encourage them to just do it.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Is My Child Overtired?: The Sleep Solution for Raising Happier, Healthier Children.” Email him at pdnews@mdedge.com.

Sleep has begun to emerge from the shadows to gain its rightful place in the health pantheon. With this emergence has come a motley group of physicians and self-proclaimed experts (myself included) eager to share their anecdotal evidence and opinions on how new parents can shorten the inevitable and often painfully slow process of settling in.

a-fitz/Stockphoto

A study in the May 2018 Journal of Pediatrics is an attempt to provide some data-driven guidance for sleep-deprived parents and their physician-advisors (“Real-World Implementation of Infant Behavioral Sleep Interventions: Results of a Parental Survey”). Using the responses from 652 parents who participated in a Facebook peer support group, the investigators created four categories of behavior sleep intervention for the parents of infants a mean age of 6 months: Modified extinction in which parents left the room and returned to briefly reassure the infant at intervals ranging from 5 to 25 minutes; unmodified extinction in which the parents let the infant cry it out; parental presence with support in which the parents remained in the room and interacted with the child; and parental presence without support. Extinction, both modified and unmodified (50% and 35%), was far and away the most frequently used method.

There was little difference in the effectiveness of the four strategies. By 2 weeks, 79% of the parents reported success, and the interventions were successfully discontinued in a mean and mode of 7 days. Not surprisingly, with success came reduced parental stress, as well as more consistent bedtime routines and smoother transitions to sleep.

When choosing a behavioral sleep intervention to suggest, I have tried to consider what I have learned about each family’s personality in the few months I have gotten to know them. But I have always been a big fan of extinction. And I suspect that my bias is simply a reflection of my no-nonsense, let’s-get-it-done-now personality. The results of this new study suggests that my poorly disguised pessimism about parental presence strategies may have discouraged some parents from trying an intervention that might have been successful for them.

The good news is that all four strategies can be successful. The problem is helping parents find the time and energy required to make any intervention successful. In the short term, extinction or parental presence is likely to mean less sleep for the parents. If work schedules and other family stressors already have drained a family’s energy reserves, it may not be the right time to try an intervention. When it becomes clear that there is never going to be right time, it is time for a frank discussion with the family about rearranging their priorities.

Behavioral sleep interventions require consistency and a family must be prepared to commit at least a week of uninterrupted evenings to get the job done. Business trips, visitors, and social engagements must take a back seat.

Extinction strategies are going to involve some crying, and while as pediatricians, we have developed the ability to buffer ourselves from crying (ignore really isn’t the right word), we must accept that listening to one’s child is too painful for some parents. When only one parent can’t tolerate the crying, the solution may be having that parent leave the home on the intervention evenings. When both parents share the vulnerability, the better answer is a parental presence strategy.

Although this study was small with a self-selected group of parents, the good news is that behavioral sleep intervention can work. We need to share the news with young families and encourage them to just do it.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “Is My Child Overtired?: The Sleep Solution for Raising Happier, Healthier Children.” Email him at pdnews@mdedge.com.

Presenter

Leonard Feldman, MD, SFHM

Session summary

In the current climate of increasing national health care expenditures, the Journal of Hospital Medicine continues to expand its series “Things We Do for No Reason” to shed light on areas for improvement in the delivery of high-value care. Physicians, however, continue to practice low value care because of practice habits and lack of cost transparency. In keeping with the spirit of the journal’s series, three low-value practices were highlighted in this HM18 session, including the benefits of high-flow nasal cannula (HFNC) oxygen therapy, the value of serum albumin and prealbumin in malnutrition, and the use of nebulized versus inhaler albuterol.

HFNC oxygen therapy has become a widespread practice internationally, with large variations in implementation across all age ranges. In bronchiolitic infants, variations in time of implementation, duration of therapy, weaning policies, and outcome measures have yielded mixed results to date. Many studies are still underway, but current literature has not shown significant benefits of starting HFNC early in the illness process, and infants receiving HFNC have not had better outcomes than those who received standard therapy (low-flow nasal cannula).

Serum albumin and prealbumin are often cited as markers of malnutrition. In patients on tube feeds, such as those with cerebral palsy and complex medical conditions, current literature shows no benefit in the use of these lab markers for screening or for following to assess improvement. In addition, patients with eating disorders do not have significant correlation of their nutritive status with these markers. Therefore, the use of these labs for screening of malnutrition is of little if any value.

Finally, when comparing albuterol delivery systems, there has been no proof that nebulized albuterol is any better than metered dose inhalers (MDI) in its effect. As long as appropriate dosing of MDIs is done, the benefits are the same. In addition, side effects are fewer, and the length of stay in the ED is shorter. The more a family uses MDI inhalers, the better their technique. Studies have shown it takes approximately three attempts at using an MDI to get the technique correct, so inpatient MDI use would also decrease user error in the outpatient setting.
 

Key takeaways for HM

• Practice habits, lack of transparency of costs, and regional training lead to low value care practices.
• Early introduction of high-flow nasal cannula in hospitalization of an infant with bronchiolitis has not been shown to decrease length of stay or severity outcomes, according to currently available data.
• Serum albumin and prealbumin have little to no benefit in screening of malnutrition.
• Nebulized albuterol has not been proven to be more beneficial that MDI albuterol at appropriate doses.
• Repeat MDI administration has been shown to positively affect user administration techniques.
• MDI albuterol use has fewer side effects and decreased ED length of stay, compared with nebulized albuterol.

Dr. Schwenk is an associate professor of pediatrics at the University of Louisville (Ky.) and a pediatric hospitalist at Norton Children’s Hospital, Louisville.

Presenter

Leonard Feldman, MD, SFHM

Session summary

In the current climate of increasing national health care expenditures, the Journal of Hospital Medicine continues to expand its series “Things We Do for No Reason” to shed light on areas for improvement in the delivery of high-value care. Physicians, however, continue to practice low value care because of practice habits and lack of cost transparency. In keeping with the spirit of the journal’s series, three low-value practices were highlighted in this HM18 session, including the benefits of high-flow nasal cannula (HFNC) oxygen therapy, the value of serum albumin and prealbumin in malnutrition, and the use of nebulized versus inhaler albuterol.

HFNC oxygen therapy has become a widespread practice internationally, with large variations in implementation across all age ranges. In bronchiolitic infants, variations in time of implementation, duration of therapy, weaning policies, and outcome measures have yielded mixed results to date. Many studies are still underway, but current literature has not shown significant benefits of starting HFNC early in the illness process, and infants receiving HFNC have not had better outcomes than those who received standard therapy (low-flow nasal cannula).

Serum albumin and prealbumin are often cited as markers of malnutrition. In patients on tube feeds, such as those with cerebral palsy and complex medical conditions, current literature shows no benefit in the use of these lab markers for screening or for following to assess improvement. In addition, patients with eating disorders do not have significant correlation of their nutritive status with these markers. Therefore, the use of these labs for screening of malnutrition is of little if any value.

Finally, when comparing albuterol delivery systems, there has been no proof that nebulized albuterol is any better than metered dose inhalers (MDI) in its effect. As long as appropriate dosing of MDIs is done, the benefits are the same. In addition, side effects are fewer, and the length of stay in the ED is shorter. The more a family uses MDI inhalers, the better their technique. Studies have shown it takes approximately three attempts at using an MDI to get the technique correct, so inpatient MDI use would also decrease user error in the outpatient setting.
 

Key takeaways for HM

• Practice habits, lack of transparency of costs, and regional training lead to low value care practices.
• Early introduction of high-flow nasal cannula in hospitalization of an infant with bronchiolitis has not been shown to decrease length of stay or severity outcomes, according to currently available data.
• Serum albumin and prealbumin have little to no benefit in screening of malnutrition.
• Nebulized albuterol has not been proven to be more beneficial that MDI albuterol at appropriate doses.
• Repeat MDI administration has been shown to positively affect user administration techniques.
• MDI albuterol use has fewer side effects and decreased ED length of stay, compared with nebulized albuterol.

Dr. Schwenk is an associate professor of pediatrics at the University of Louisville (Ky.) and a pediatric hospitalist at Norton Children’s Hospital, Louisville.

Presenter

Leonard Feldman, MD, SFHM

Session summary

In the current climate of increasing national health care expenditures, the Journal of Hospital Medicine continues to expand its series “Things We Do for No Reason” to shed light on areas for improvement in the delivery of high-value care. Physicians, however, continue to practice low value care because of practice habits and lack of cost transparency. In keeping with the spirit of the journal’s series, three low-value practices were highlighted in this HM18 session, including the benefits of high-flow nasal cannula (HFNC) oxygen therapy, the value of serum albumin and prealbumin in malnutrition, and the use of nebulized versus inhaler albuterol.

HFNC oxygen therapy has become a widespread practice internationally, with large variations in implementation across all age ranges. In bronchiolitic infants, variations in time of implementation, duration of therapy, weaning policies, and outcome measures have yielded mixed results to date. Many studies are still underway, but current literature has not shown significant benefits of starting HFNC early in the illness process, and infants receiving HFNC have not had better outcomes than those who received standard therapy (low-flow nasal cannula).

Serum albumin and prealbumin are often cited as markers of malnutrition. In patients on tube feeds, such as those with cerebral palsy and complex medical conditions, current literature shows no benefit in the use of these lab markers for screening or for following to assess improvement. In addition, patients with eating disorders do not have significant correlation of their nutritive status with these markers. Therefore, the use of these labs for screening of malnutrition is of little if any value.

Finally, when comparing albuterol delivery systems, there has been no proof that nebulized albuterol is any better than metered dose inhalers (MDI) in its effect. As long as appropriate dosing of MDIs is done, the benefits are the same. In addition, side effects are fewer, and the length of stay in the ED is shorter. The more a family uses MDI inhalers, the better their technique. Studies have shown it takes approximately three attempts at using an MDI to get the technique correct, so inpatient MDI use would also decrease user error in the outpatient setting.
 

Key takeaways for HM

• Practice habits, lack of transparency of costs, and regional training lead to low value care practices.
• Early introduction of high-flow nasal cannula in hospitalization of an infant with bronchiolitis has not been shown to decrease length of stay or severity outcomes, according to currently available data.
• Serum albumin and prealbumin have little to no benefit in screening of malnutrition.
• Nebulized albuterol has not been proven to be more beneficial that MDI albuterol at appropriate doses.
• Repeat MDI administration has been shown to positively affect user administration techniques.
• MDI albuterol use has fewer side effects and decreased ED length of stay, compared with nebulized albuterol.

Dr. Schwenk is an associate professor of pediatrics at the University of Louisville (Ky.) and a pediatric hospitalist at Norton Children’s Hospital, Louisville.

Spinal muscular atrophy (SMA) is now among the disorders officially included in the Recommended Uniform Screening Panel (RUSP), which is used by state public health departments to screen newborns for genetic disorders.

Secretary of the Department of Health and Human Services Alex M. Azar II formally added SMA to the panel July 2 on the recommendation of the Advisory Committee on Heritable Disorders in Newborns and Children.

AngelIce/Thinkstock

“Adding SMA to the list will help ensure that babies born with SMA are identified, so that they have the opportunity to benefit from early treatment and intervention,” according to a statement from the Muscular Dystrophy Association about the decision. “This testing can also provide families with a genetic diagnosis – information that often is required to determine whether their child is eligible to participate in clinical trials.”

Adding SMA to the RUSP does not mean states must screen newborns for the disorder. Each state’s public health apparatus decides independently whether to accept the recommendation and which disorders on the RUSP to screen for. Most states screen for most disorders on the RUSP. Evidence compiled by the advisory committee suggested wide variation in resources, infrastructure, funding, and time to implementation among states.

An estimated 1 in 11,000 newborns have SMA, a disorder caused by mutations in the survival motor neuron 1 (SMN1) gene. SMA affects motor neurons in the brain stem and spinal cord leading to motor weakness and atrophy. The only treatment for SMA had been palliative care until the Food and Drug Administration approved nusinersen (Spinraza) for the disorder in December 2016, although the drug’s approval has raised some ethical questions.^1-3

After reviewing the evidence at their February 8, 2018 meeting, the advisory committee recommended the addition of spinal muscular atrophy screening to the RUSP in a March 8, 2018, letter from committee chair Joseph A. Bocchini Jr., MD, who is a professor and the chairman of the department of pediatrics at Louisiana State University Health in Shreveport.

Secretary Azar accepted the recommendation based on the evidence the committee provided; he also requested a follow-up report within 2 years “describing the status of implementing newborn screening for SMA and clinical outcomes of early treatment, including any potential harms, for infants diagnosed with SMA.”

The advisory committee makes its recommendations to the HHS on which heritable disorders to include in the RUSP after they have assessed a systematic, evidence-based review assigned by the committee to an external independent group. Alex R. Kemper, MD, MPH, a professor of pediatrics at the Ohio State University and division chief of ambulatory pediatrics at Nationwide Children’s Hospital, both in Columbus, led the review group for SMA. Dr. Kemper is also deputy editor of the journal Pediatrics and a member of the U.S. Preventive Services Task Force.

Wikimedia Commons/WWsgConnect/CC-SA 4.0

According to Secretary Azar’s summary in his July 2, 2018, letter of acceptance, the evidence review suggested that “early screening and treatment can lead to decreased mortality for individuals with SMA and improved motor milestones.”

Dr. Kemper elaborated in an interview that, “SMA can be detected through newborn screening, and treatment is now available that can not only reduce the risk of death but decrease the development of neurologic impairment. As with adding any condition to newborn screening, public health laboratories will need to develop strategies to incorporate the screening test. The current FDA-approved treatment, nusinersen, is delivered by lumbar puncture into the spinal fluid. In addition, there are exciting advances in gene therapy leading to new treatment approaches.”

Approximately 95% of SMA cases result from the deletion of exon 7 from both alleles of SMN1. (Other rarer cases are caused by mutations in different genes.) Without the SMN protein produced by SMN1, a person gradually loses muscle function.

A similar gene, SMN2, also can produce the SMN protein but in much lower amounts, typically less than 10% of what a person needs. People can, however, have multiple copies of SMN2, which can produce slightly more SMN protein for a slower disease process.

The five types of spinal muscular atrophy are determined according to symptom onset, which directly correlates with disorder severity and prognosis. Just over half (54%) of SMA cases are Type I, in which progressive weakness occurs over the first 6 months of life and results in early death. Only 18% of children with Type I live past age 4 years, and 68% die by age 2 years. Type 0 is rarer but more severe, usually causing fetal loss or early infant death.

Type II represents 18% of SMA cases and causes progressive weakness by age 15 months. Most people with Type II survive to their 30s but then experience respiratory failure and rarely reach their fourth decade. Individuals with Types III and IV typically have a normal lifespan and only begin to see progressive muscle weakness after 1 year old or in adulthood.

Dr. Kemper’s group focused on the three types diagnosed in infancy: types I, II, and III.

Dr. Kemper emphasized in an interview that “it will be critical to make sure that infants diagnosed with SMA through newborn screening receive follow-up shortly afterward to determine whether they would benefit from nusinersen. More information is needed about the long-term outcomes of those infants who begin treatment following newborn screening so we not only know about outcomes in later childhood and adolescence but treatment approaches can be further refined and personalized.”

Nusinersen works by altering the splicing of precursor messenger RNA in SMN2 so that the mRNA strands are longer, which thereby increases how much SMN protein is produced. Concerns about the medication, however, have included its cost – $750,000 in the first year and $375,000 every following year for life – and potential adverse events from repeated administration. Nusinersen is injected into the spinal canal four times in the first year and then once annually, and the painful injections require patient immobilization. Potential adverse events include thrombocytopenia and nephrotoxicity, along with potential complications from repeated lumbar punctures over time.²

Other concerns about the drug include its limited evidence base, lack of long-term data, associated costs with administration (for example, travel costs), the potential for patients taking nusinersen to be excluded from future clinical trials on other treatments, and ensuring parents have enough information on the drug’s limitations and potential risks to provide adequate informed consent.²

Yet evidence to date is favorable in children with early onset. Dr. Bocchini wrote in the letter to Secretary Azar that “limited data suggest that treatment effect is greater when the treatment is initiated before symptoms develop and when the individual has more copies of SMN2.”

Dr. Kemper’s group concluded that screening can detect SMA in newborns and that treatment can modify disease course. “Grey literature suggests those with total disease duration less than or equal to 12 weeks before nusinersen treatment were more likely to have better outcomes than those with longer periods of disease duration.”

“Presymptomatic treatment alters the natural history” of the disorder, the group found, although outcome data past 1 year of age are not yet available. Based on findings from a New York pilot program, they predicted that nationwide newborn screening would avert 33 deaths and 48 cases of children who were dependent on a ventilator among an annual cohort of 4 million births.

At the time of the evidence review, Massachusetts, Minnesota, Missouri, North Carolina, New York, Utah, and Wisconsin initiated pilot programs or whole-population mandated screening for SMA. Of the three states that reported costs, all reported costs at $1 or less per screen.

The research for the evidence review was funded by a Health Resources and Services Administration grant to Duke University, Durham, N.C. No disclosures were provided for evidence review group members.
 

References

1. Gene Ther. 2017 Sep;24(9):534-8.

2. JAMA Intern Med. 2018 Jun 1;178(6):743-44.

3. JAMA Pediatr. 2018 Feb 1;172(2):188-92.

Spinal muscular atrophy (SMA) is now among the disorders officially included in the Recommended Uniform Screening Panel (RUSP), which is used by state public health departments to screen newborns for genetic disorders.

Secretary of the Department of Health and Human Services Alex M. Azar II formally added SMA to the panel July 2 on the recommendation of the Advisory Committee on Heritable Disorders in Newborns and Children.

AngelIce/Thinkstock

“Adding SMA to the list will help ensure that babies born with SMA are identified, so that they have the opportunity to benefit from early treatment and intervention,” according to a statement from the Muscular Dystrophy Association about the decision. “This testing can also provide families with a genetic diagnosis – information that often is required to determine whether their child is eligible to participate in clinical trials.”

Adding SMA to the RUSP does not mean states must screen newborns for the disorder. Each state’s public health apparatus decides independently whether to accept the recommendation and which disorders on the RUSP to screen for. Most states screen for most disorders on the RUSP. Evidence compiled by the advisory committee suggested wide variation in resources, infrastructure, funding, and time to implementation among states.

An estimated 1 in 11,000 newborns have SMA, a disorder caused by mutations in the survival motor neuron 1 (SMN1) gene. SMA affects motor neurons in the brain stem and spinal cord leading to motor weakness and atrophy. The only treatment for SMA had been palliative care until the Food and Drug Administration approved nusinersen (Spinraza) for the disorder in December 2016, although the drug’s approval has raised some ethical questions.^1-3

After reviewing the evidence at their February 8, 2018 meeting, the advisory committee recommended the addition of spinal muscular atrophy screening to the RUSP in a March 8, 2018, letter from committee chair Joseph A. Bocchini Jr., MD, who is a professor and the chairman of the department of pediatrics at Louisiana State University Health in Shreveport.

Secretary Azar accepted the recommendation based on the evidence the committee provided; he also requested a follow-up report within 2 years “describing the status of implementing newborn screening for SMA and clinical outcomes of early treatment, including any potential harms, for infants diagnosed with SMA.”

The advisory committee makes its recommendations to the HHS on which heritable disorders to include in the RUSP after they have assessed a systematic, evidence-based review assigned by the committee to an external independent group. Alex R. Kemper, MD, MPH, a professor of pediatrics at the Ohio State University and division chief of ambulatory pediatrics at Nationwide Children’s Hospital, both in Columbus, led the review group for SMA. Dr. Kemper is also deputy editor of the journal Pediatrics and a member of the U.S. Preventive Services Task Force.

Wikimedia Commons/WWsgConnect/CC-SA 4.0

According to Secretary Azar’s summary in his July 2, 2018, letter of acceptance, the evidence review suggested that “early screening and treatment can lead to decreased mortality for individuals with SMA and improved motor milestones.”

Dr. Kemper elaborated in an interview that, “SMA can be detected through newborn screening, and treatment is now available that can not only reduce the risk of death but decrease the development of neurologic impairment. As with adding any condition to newborn screening, public health laboratories will need to develop strategies to incorporate the screening test. The current FDA-approved treatment, nusinersen, is delivered by lumbar puncture into the spinal fluid. In addition, there are exciting advances in gene therapy leading to new treatment approaches.”

Approximately 95% of SMA cases result from the deletion of exon 7 from both alleles of SMN1. (Other rarer cases are caused by mutations in different genes.) Without the SMN protein produced by SMN1, a person gradually loses muscle function.

A similar gene, SMN2, also can produce the SMN protein but in much lower amounts, typically less than 10% of what a person needs. People can, however, have multiple copies of SMN2, which can produce slightly more SMN protein for a slower disease process.

The five types of spinal muscular atrophy are determined according to symptom onset, which directly correlates with disorder severity and prognosis. Just over half (54%) of SMA cases are Type I, in which progressive weakness occurs over the first 6 months of life and results in early death. Only 18% of children with Type I live past age 4 years, and 68% die by age 2 years. Type 0 is rarer but more severe, usually causing fetal loss or early infant death.

Type II represents 18% of SMA cases and causes progressive weakness by age 15 months. Most people with Type II survive to their 30s but then experience respiratory failure and rarely reach their fourth decade. Individuals with Types III and IV typically have a normal lifespan and only begin to see progressive muscle weakness after 1 year old or in adulthood.

Dr. Kemper’s group focused on the three types diagnosed in infancy: types I, II, and III.

Dr. Kemper emphasized in an interview that “it will be critical to make sure that infants diagnosed with SMA through newborn screening receive follow-up shortly afterward to determine whether they would benefit from nusinersen. More information is needed about the long-term outcomes of those infants who begin treatment following newborn screening so we not only know about outcomes in later childhood and adolescence but treatment approaches can be further refined and personalized.”

Nusinersen works by altering the splicing of precursor messenger RNA in SMN2 so that the mRNA strands are longer, which thereby increases how much SMN protein is produced. Concerns about the medication, however, have included its cost – $750,000 in the first year and $375,000 every following year for life – and potential adverse events from repeated administration. Nusinersen is injected into the spinal canal four times in the first year and then once annually, and the painful injections require patient immobilization. Potential adverse events include thrombocytopenia and nephrotoxicity, along with potential complications from repeated lumbar punctures over time.²

Other concerns about the drug include its limited evidence base, lack of long-term data, associated costs with administration (for example, travel costs), the potential for patients taking nusinersen to be excluded from future clinical trials on other treatments, and ensuring parents have enough information on the drug’s limitations and potential risks to provide adequate informed consent.²

Yet evidence to date is favorable in children with early onset. Dr. Bocchini wrote in the letter to Secretary Azar that “limited data suggest that treatment effect is greater when the treatment is initiated before symptoms develop and when the individual has more copies of SMN2.”

Dr. Kemper’s group concluded that screening can detect SMA in newborns and that treatment can modify disease course. “Grey literature suggests those with total disease duration less than or equal to 12 weeks before nusinersen treatment were more likely to have better outcomes than those with longer periods of disease duration.”

“Presymptomatic treatment alters the natural history” of the disorder, the group found, although outcome data past 1 year of age are not yet available. Based on findings from a New York pilot program, they predicted that nationwide newborn screening would avert 33 deaths and 48 cases of children who were dependent on a ventilator among an annual cohort of 4 million births.

At the time of the evidence review, Massachusetts, Minnesota, Missouri, North Carolina, New York, Utah, and Wisconsin initiated pilot programs or whole-population mandated screening for SMA. Of the three states that reported costs, all reported costs at $1 or less per screen.

The research for the evidence review was funded by a Health Resources and Services Administration grant to Duke University, Durham, N.C. No disclosures were provided for evidence review group members.
 

References

1. Gene Ther. 2017 Sep;24(9):534-8.

2. JAMA Intern Med. 2018 Jun 1;178(6):743-44.

3. JAMA Pediatr. 2018 Feb 1;172(2):188-92.

Spinal muscular atrophy (SMA) is now among the disorders officially included in the Recommended Uniform Screening Panel (RUSP), which is used by state public health departments to screen newborns for genetic disorders.

Secretary of the Department of Health and Human Services Alex M. Azar II formally added SMA to the panel July 2 on the recommendation of the Advisory Committee on Heritable Disorders in Newborns and Children.

AngelIce/Thinkstock

“Adding SMA to the list will help ensure that babies born with SMA are identified, so that they have the opportunity to benefit from early treatment and intervention,” according to a statement from the Muscular Dystrophy Association about the decision. “This testing can also provide families with a genetic diagnosis – information that often is required to determine whether their child is eligible to participate in clinical trials.”

Adding SMA to the RUSP does not mean states must screen newborns for the disorder. Each state’s public health apparatus decides independently whether to accept the recommendation and which disorders on the RUSP to screen for. Most states screen for most disorders on the RUSP. Evidence compiled by the advisory committee suggested wide variation in resources, infrastructure, funding, and time to implementation among states.

An estimated 1 in 11,000 newborns have SMA, a disorder caused by mutations in the survival motor neuron 1 (SMN1) gene. SMA affects motor neurons in the brain stem and spinal cord leading to motor weakness and atrophy. The only treatment for SMA had been palliative care until the Food and Drug Administration approved nusinersen (Spinraza) for the disorder in December 2016, although the drug’s approval has raised some ethical questions.^1-3

After reviewing the evidence at their February 8, 2018 meeting, the advisory committee recommended the addition of spinal muscular atrophy screening to the RUSP in a March 8, 2018, letter from committee chair Joseph A. Bocchini Jr., MD, who is a professor and the chairman of the department of pediatrics at Louisiana State University Health in Shreveport.

Secretary Azar accepted the recommendation based on the evidence the committee provided; he also requested a follow-up report within 2 years “describing the status of implementing newborn screening for SMA and clinical outcomes of early treatment, including any potential harms, for infants diagnosed with SMA.”

The advisory committee makes its recommendations to the HHS on which heritable disorders to include in the RUSP after they have assessed a systematic, evidence-based review assigned by the committee to an external independent group. Alex R. Kemper, MD, MPH, a professor of pediatrics at the Ohio State University and division chief of ambulatory pediatrics at Nationwide Children’s Hospital, both in Columbus, led the review group for SMA. Dr. Kemper is also deputy editor of the journal Pediatrics and a member of the U.S. Preventive Services Task Force.

Wikimedia Commons/WWsgConnect/CC-SA 4.0

According to Secretary Azar’s summary in his July 2, 2018, letter of acceptance, the evidence review suggested that “early screening and treatment can lead to decreased mortality for individuals with SMA and improved motor milestones.”

Dr. Kemper elaborated in an interview that, “SMA can be detected through newborn screening, and treatment is now available that can not only reduce the risk of death but decrease the development of neurologic impairment. As with adding any condition to newborn screening, public health laboratories will need to develop strategies to incorporate the screening test. The current FDA-approved treatment, nusinersen, is delivered by lumbar puncture into the spinal fluid. In addition, there are exciting advances in gene therapy leading to new treatment approaches.”

Approximately 95% of SMA cases result from the deletion of exon 7 from both alleles of SMN1. (Other rarer cases are caused by mutations in different genes.) Without the SMN protein produced by SMN1, a person gradually loses muscle function.

A similar gene, SMN2, also can produce the SMN protein but in much lower amounts, typically less than 10% of what a person needs. People can, however, have multiple copies of SMN2, which can produce slightly more SMN protein for a slower disease process.

The five types of spinal muscular atrophy are determined according to symptom onset, which directly correlates with disorder severity and prognosis. Just over half (54%) of SMA cases are Type I, in which progressive weakness occurs over the first 6 months of life and results in early death. Only 18% of children with Type I live past age 4 years, and 68% die by age 2 years. Type 0 is rarer but more severe, usually causing fetal loss or early infant death.

Type II represents 18% of SMA cases and causes progressive weakness by age 15 months. Most people with Type II survive to their 30s but then experience respiratory failure and rarely reach their fourth decade. Individuals with Types III and IV typically have a normal lifespan and only begin to see progressive muscle weakness after 1 year old or in adulthood.

Dr. Kemper’s group focused on the three types diagnosed in infancy: types I, II, and III.

Dr. Kemper emphasized in an interview that “it will be critical to make sure that infants diagnosed with SMA through newborn screening receive follow-up shortly afterward to determine whether they would benefit from nusinersen. More information is needed about the long-term outcomes of those infants who begin treatment following newborn screening so we not only know about outcomes in later childhood and adolescence but treatment approaches can be further refined and personalized.”

Nusinersen works by altering the splicing of precursor messenger RNA in SMN2 so that the mRNA strands are longer, which thereby increases how much SMN protein is produced. Concerns about the medication, however, have included its cost – $750,000 in the first year and $375,000 every following year for life – and potential adverse events from repeated administration. Nusinersen is injected into the spinal canal four times in the first year and then once annually, and the painful injections require patient immobilization. Potential adverse events include thrombocytopenia and nephrotoxicity, along with potential complications from repeated lumbar punctures over time.²

Other concerns about the drug include its limited evidence base, lack of long-term data, associated costs with administration (for example, travel costs), the potential for patients taking nusinersen to be excluded from future clinical trials on other treatments, and ensuring parents have enough information on the drug’s limitations and potential risks to provide adequate informed consent.²

Yet evidence to date is favorable in children with early onset. Dr. Bocchini wrote in the letter to Secretary Azar that “limited data suggest that treatment effect is greater when the treatment is initiated before symptoms develop and when the individual has more copies of SMN2.”

Dr. Kemper’s group concluded that screening can detect SMA in newborns and that treatment can modify disease course. “Grey literature suggests those with total disease duration less than or equal to 12 weeks before nusinersen treatment were more likely to have better outcomes than those with longer periods of disease duration.”

“Presymptomatic treatment alters the natural history” of the disorder, the group found, although outcome data past 1 year of age are not yet available. Based on findings from a New York pilot program, they predicted that nationwide newborn screening would avert 33 deaths and 48 cases of children who were dependent on a ventilator among an annual cohort of 4 million births.

At the time of the evidence review, Massachusetts, Minnesota, Missouri, North Carolina, New York, Utah, and Wisconsin initiated pilot programs or whole-population mandated screening for SMA. Of the three states that reported costs, all reported costs at $1 or less per screen.

The research for the evidence review was funded by a Health Resources and Services Administration grant to Duke University, Durham, N.C. No disclosures were provided for evidence review group members.
 

References

1. Gene Ther. 2017 Sep;24(9):534-8.

2. JAMA Intern Med. 2018 Jun 1;178(6):743-44.

3. JAMA Pediatr. 2018 Feb 1;172(2):188-92.

MALMO, SWEDEN – Human papillomavirus (HPV) vaccination in Finnish girls aged 11-15 years was not associated with significantly higher risk of any of 38 potential adverse outcomes in a nationwide, retrospective cohort study.

Bruce Jancin/MDedge News

“Anxiety and fear regarding adverse events are still very much alive and are associated with lack of acceptance of HPV vaccination,” Jozica Skufca, DVM, MIPH, observed while presenting the study findings at the annual meeting of the European Society for Paediatric Infectious Diseases.

“These results contribute valid evidence to combat public skepticism, anxiety, fears of adverse events, and possible opposition to HPV vaccination and consequently can contribute to increase HPV vaccination coverage in Finland as well as elsewhere,” added Dr. Skufca, who conducted this research while at the Finnish National Institute for Health and Welfare but is now an epidemiologist at P95, a privately held epidemiology and pharmacovigilance consulting firm in Heverlee, Belgium.

Finland introduced the bivalent HPV vaccine known as Cervarix, which is directed against HPV types 16 and 18, into the nation’s vaccination program in November 2013. The target population were girls aged 11-13 years, with catch-up vaccination at ages 14-15 years until 2015.

Dr. Skufca utilized Finland’s comprehensive system of national health care registries to conduct a study of all 240,605 Finnish girls aged 11-15 years who were eligible for the bivalent HPV vaccine from November 2013 to December 2016. Only 56% of the target population, or 134,615 girls, were actually vaccinated. All were subsequently followed for more than a year.

The investigators compared vaccinated and unvaccinated groups in terms of the subsequent rates of 38 selected outcomes of national and international interest. These included celiac disease, chronic fatigue syndrome, type 1 diabetes, Guillain-Barré syndrome, postural orthostatic tachycardia syndrome, ulcerative colitis, venous thromboembolism, psoriasis, vitiligo, scleroderma, autism, poyarteritis nodosa, asthma, Raynaud’s disease, systemic lupus erythematosus, Bell’s palsy, polycystic ovaries, juvenile arthritis, Hashimoto’s disease, and many others.

HPV vaccination rates varied considerably between hospital districts, so the results were adjusted for that potential confounder. Risks also were adjusted for the number of hospital visits 1-2 years prior to vaccination, because healthier girls – those with fewer hospital visits – turned out to be more likely to get vaccinated.

The study’s main result was that HPV vaccination wasn’t associated with a significantly higher risk of any of the 38 adverse outcomes. To the contrary, vaccination was associated with significantly reduced risk of several of them: The risk of chronic fatigue syndrome was reduced by 25%, epilepsy and recurrent seizures were reduced by 28%, the risk of Henoch-Schönlein purpura was an adjusted 52% lower in children vaccinated against HPV, and the risk of malaise and fatigue was reduced by 24%.

Dr. Skufca drew particular attention to the 400% increased risk of Guillain-Barré syndrome in vaccinated children. While this may look impressive, it wasn’t a statistically significant difference. Guillain-Barré was a rare event, with only six cases occurring during 186,934 person-years of follow-up of vaccinated individuals and a single case in unvaccinated girls. Two cases occurred within 180 days after vaccination, for an adjusted 200% increase in risk, which was nonsignificant.

bjancin@mdedge.com

MALMO, SWEDEN – Human papillomavirus (HPV) vaccination in Finnish girls aged 11-15 years was not associated with significantly higher risk of any of 38 potential adverse outcomes in a nationwide, retrospective cohort study.

Bruce Jancin/MDedge News

“Anxiety and fear regarding adverse events are still very much alive and are associated with lack of acceptance of HPV vaccination,” Jozica Skufca, DVM, MIPH, observed while presenting the study findings at the annual meeting of the European Society for Paediatric Infectious Diseases.

“These results contribute valid evidence to combat public skepticism, anxiety, fears of adverse events, and possible opposition to HPV vaccination and consequently can contribute to increase HPV vaccination coverage in Finland as well as elsewhere,” added Dr. Skufca, who conducted this research while at the Finnish National Institute for Health and Welfare but is now an epidemiologist at P95, a privately held epidemiology and pharmacovigilance consulting firm in Heverlee, Belgium.

Finland introduced the bivalent HPV vaccine known as Cervarix, which is directed against HPV types 16 and 18, into the nation’s vaccination program in November 2013. The target population were girls aged 11-13 years, with catch-up vaccination at ages 14-15 years until 2015.

Dr. Skufca utilized Finland’s comprehensive system of national health care registries to conduct a study of all 240,605 Finnish girls aged 11-15 years who were eligible for the bivalent HPV vaccine from November 2013 to December 2016. Only 56% of the target population, or 134,615 girls, were actually vaccinated. All were subsequently followed for more than a year.

The investigators compared vaccinated and unvaccinated groups in terms of the subsequent rates of 38 selected outcomes of national and international interest. These included celiac disease, chronic fatigue syndrome, type 1 diabetes, Guillain-Barré syndrome, postural orthostatic tachycardia syndrome, ulcerative colitis, venous thromboembolism, psoriasis, vitiligo, scleroderma, autism, poyarteritis nodosa, asthma, Raynaud’s disease, systemic lupus erythematosus, Bell’s palsy, polycystic ovaries, juvenile arthritis, Hashimoto’s disease, and many others.

HPV vaccination rates varied considerably between hospital districts, so the results were adjusted for that potential confounder. Risks also were adjusted for the number of hospital visits 1-2 years prior to vaccination, because healthier girls – those with fewer hospital visits – turned out to be more likely to get vaccinated.

The study’s main result was that HPV vaccination wasn’t associated with a significantly higher risk of any of the 38 adverse outcomes. To the contrary, vaccination was associated with significantly reduced risk of several of them: The risk of chronic fatigue syndrome was reduced by 25%, epilepsy and recurrent seizures were reduced by 28%, the risk of Henoch-Schönlein purpura was an adjusted 52% lower in children vaccinated against HPV, and the risk of malaise and fatigue was reduced by 24%.

Dr. Skufca drew particular attention to the 400% increased risk of Guillain-Barré syndrome in vaccinated children. While this may look impressive, it wasn’t a statistically significant difference. Guillain-Barré was a rare event, with only six cases occurring during 186,934 person-years of follow-up of vaccinated individuals and a single case in unvaccinated girls. Two cases occurred within 180 days after vaccination, for an adjusted 200% increase in risk, which was nonsignificant.

bjancin@mdedge.com

MALMO, SWEDEN – Human papillomavirus (HPV) vaccination in Finnish girls aged 11-15 years was not associated with significantly higher risk of any of 38 potential adverse outcomes in a nationwide, retrospective cohort study.

Bruce Jancin/MDedge News

“Anxiety and fear regarding adverse events are still very much alive and are associated with lack of acceptance of HPV vaccination,” Jozica Skufca, DVM, MIPH, observed while presenting the study findings at the annual meeting of the European Society for Paediatric Infectious Diseases.

“These results contribute valid evidence to combat public skepticism, anxiety, fears of adverse events, and possible opposition to HPV vaccination and consequently can contribute to increase HPV vaccination coverage in Finland as well as elsewhere,” added Dr. Skufca, who conducted this research while at the Finnish National Institute for Health and Welfare but is now an epidemiologist at P95, a privately held epidemiology and pharmacovigilance consulting firm in Heverlee, Belgium.

Finland introduced the bivalent HPV vaccine known as Cervarix, which is directed against HPV types 16 and 18, into the nation’s vaccination program in November 2013. The target population were girls aged 11-13 years, with catch-up vaccination at ages 14-15 years until 2015.

Dr. Skufca utilized Finland’s comprehensive system of national health care registries to conduct a study of all 240,605 Finnish girls aged 11-15 years who were eligible for the bivalent HPV vaccine from November 2013 to December 2016. Only 56% of the target population, or 134,615 girls, were actually vaccinated. All were subsequently followed for more than a year.

The investigators compared vaccinated and unvaccinated groups in terms of the subsequent rates of 38 selected outcomes of national and international interest. These included celiac disease, chronic fatigue syndrome, type 1 diabetes, Guillain-Barré syndrome, postural orthostatic tachycardia syndrome, ulcerative colitis, venous thromboembolism, psoriasis, vitiligo, scleroderma, autism, poyarteritis nodosa, asthma, Raynaud’s disease, systemic lupus erythematosus, Bell’s palsy, polycystic ovaries, juvenile arthritis, Hashimoto’s disease, and many others.

HPV vaccination rates varied considerably between hospital districts, so the results were adjusted for that potential confounder. Risks also were adjusted for the number of hospital visits 1-2 years prior to vaccination, because healthier girls – those with fewer hospital visits – turned out to be more likely to get vaccinated.

The study’s main result was that HPV vaccination wasn’t associated with a significantly higher risk of any of the 38 adverse outcomes. To the contrary, vaccination was associated with significantly reduced risk of several of them: The risk of chronic fatigue syndrome was reduced by 25%, epilepsy and recurrent seizures were reduced by 28%, the risk of Henoch-Schönlein purpura was an adjusted 52% lower in children vaccinated against HPV, and the risk of malaise and fatigue was reduced by 24%.

Dr. Skufca drew particular attention to the 400% increased risk of Guillain-Barré syndrome in vaccinated children. While this may look impressive, it wasn’t a statistically significant difference. Guillain-Barré was a rare event, with only six cases occurring during 186,934 person-years of follow-up of vaccinated individuals and a single case in unvaccinated girls. Two cases occurred within 180 days after vaccination, for an adjusted 200% increase in risk, which was nonsignificant.

bjancin@mdedge.com

MALMO, SWEDEN – Early identification of deep vein thrombosis in children with acute hematogenous osteomyelitis is critical given the need to plan anticoagulation management around the high likelihood that such patients will undergo multiple surgeries, Lawson A.B. Copley, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

He and his coinvestigators have identified a handful of risk factors helpful in expediting recognition of deep vein thrombosis (DVT) in children with suspected invasive infection of the musculoskeletal system.

“To improve the rate and timing of identification of DVT, we recommend performing early screening ultrasound on all children with these risk factors who are suspected of having acute hematogenous osteomyelitis,” declared Dr. Copley, professor of orthopaedic surgery and pediatrics at the University of Texas, Dallas.

Delayed diagnosis of DVT in the setting of acute hematogenous osteomyelitis (AHO) is common. Indeed, in a review of the experience at Children’s Medical Center Dallas during 2012-2014, the average time delay from ICU admission in patients suspected of having AHO to identification of DVT by ultrasound was 6.3 days.

“We’ve changed some things on the basis of that study in order to accelerate that timeline,” he explained.

Their major change was to identify actionable risk factors for DVT. This was accomplished by conducting a retrospective study of the EHR of nearly 902,000 Texas children during 2008-2016.

The study demonstrated that children with AHO complicated by DVT are, from the get-go, very different from AHO patients without DVT. They have higher illness severity of illness, are more likely to be admitted to the ICU, are prone to methicillin-resistant Staphylococcus aureus infection with prolonged bacteremia, and are much more likely to undergo multiple surgeries. Moreover, children with AHO and DVT differed substantially from other children with DVT: The dual diagnosis children lacked comorbid conditions, were prone to septic pulmonary emboli, didn’t develop postthrombotic syndrome marked by chronic venous stasis and ulcerations, and had invariably negative coagulopathy workups.

“There is no need, we feel, to perform a hypercoagulopathy workup in children with AHO complicated by DVT,” Dr. Copley said.

Drilling deeper into the data, he and his coinvestigators identified 224 new cases of DVT in the study population, for a prevalence of 2.5 per 10,000 children, along with 466 children with AHO. A total of 6% of children with AHO had DVT, and 12.1% of all children with DVT had AHO. The researchers then compared the demographics, laboratory parameters, and treatment in three cohorts: the 196 children with DVT without AHO, 28 with both AHO and DVT, and 438 with AHO without DVT.

Through this analysis, they came up with a list of risk factors warranting early screening ultrasound in children suspected of having AHO:

• An initial C-reactive protein level above 8 mg/dL, which was present in all 28 dual diagnosis children.
• ICU admission, which occurred in 19 of 28 (68%) children.
• A severity of illness score of at least 7 on a 10-point scale during the first several days in the hospital, present in 27 of the 28 children. The severity of illness scale was developed and validated by Dr. Copley and coworkers (J Pediatr Orthop. 2016 Oct 12. doi: 10.1097/BPO.0000000000000879).
• Bacteremia in the initial blood culture, present in 23 of 28 patients (82%).
• Just under 90% of the children with AHO and DVT had methicillin-resistant S. aureus, compared with 20% of those with AHO without DVT.
• Septic pulmonary emboli visualized on chest x-ray, a complication that occurred in 64% of the dual diagnosis group versus just 1% of patients with DVT without AHO.
• A band percentage of white blood cells greater than 1.5%, present in 86% of children with AHO and DVT.

More than 90% of children with AHO and DVT underwent surgery, with a mean of 2.7 surgeries per child, in contrast to the group with AHO without DVT, 55% of whom had surgery, with a mean of 0.7 surgeries per child.

Of note, there was no significant difference in the occurrence of pulmonary embolism between children with DVT without AHO versus those with DVT and AHO, with a rate of about 10% in both groups.

Dr. Copley reported having no relevant financial conflicts.

bjancin@mdedge.com

MALMO, SWEDEN – Early identification of deep vein thrombosis in children with acute hematogenous osteomyelitis is critical given the need to plan anticoagulation management around the high likelihood that such patients will undergo multiple surgeries, Lawson A.B. Copley, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

He and his coinvestigators have identified a handful of risk factors helpful in expediting recognition of deep vein thrombosis (DVT) in children with suspected invasive infection of the musculoskeletal system.

“To improve the rate and timing of identification of DVT, we recommend performing early screening ultrasound on all children with these risk factors who are suspected of having acute hematogenous osteomyelitis,” declared Dr. Copley, professor of orthopaedic surgery and pediatrics at the University of Texas, Dallas.

Delayed diagnosis of DVT in the setting of acute hematogenous osteomyelitis (AHO) is common. Indeed, in a review of the experience at Children’s Medical Center Dallas during 2012-2014, the average time delay from ICU admission in patients suspected of having AHO to identification of DVT by ultrasound was 6.3 days.

“We’ve changed some things on the basis of that study in order to accelerate that timeline,” he explained.

Their major change was to identify actionable risk factors for DVT. This was accomplished by conducting a retrospective study of the EHR of nearly 902,000 Texas children during 2008-2016.

The study demonstrated that children with AHO complicated by DVT are, from the get-go, very different from AHO patients without DVT. They have higher illness severity of illness, are more likely to be admitted to the ICU, are prone to methicillin-resistant Staphylococcus aureus infection with prolonged bacteremia, and are much more likely to undergo multiple surgeries. Moreover, children with AHO and DVT differed substantially from other children with DVT: The dual diagnosis children lacked comorbid conditions, were prone to septic pulmonary emboli, didn’t develop postthrombotic syndrome marked by chronic venous stasis and ulcerations, and had invariably negative coagulopathy workups.

“There is no need, we feel, to perform a hypercoagulopathy workup in children with AHO complicated by DVT,” Dr. Copley said.

Drilling deeper into the data, he and his coinvestigators identified 224 new cases of DVT in the study population, for a prevalence of 2.5 per 10,000 children, along with 466 children with AHO. A total of 6% of children with AHO had DVT, and 12.1% of all children with DVT had AHO. The researchers then compared the demographics, laboratory parameters, and treatment in three cohorts: the 196 children with DVT without AHO, 28 with both AHO and DVT, and 438 with AHO without DVT.

Through this analysis, they came up with a list of risk factors warranting early screening ultrasound in children suspected of having AHO:

• An initial C-reactive protein level above 8 mg/dL, which was present in all 28 dual diagnosis children.
• ICU admission, which occurred in 19 of 28 (68%) children.
• A severity of illness score of at least 7 on a 10-point scale during the first several days in the hospital, present in 27 of the 28 children. The severity of illness scale was developed and validated by Dr. Copley and coworkers (J Pediatr Orthop. 2016 Oct 12. doi: 10.1097/BPO.0000000000000879).
• Bacteremia in the initial blood culture, present in 23 of 28 patients (82%).
• Just under 90% of the children with AHO and DVT had methicillin-resistant S. aureus, compared with 20% of those with AHO without DVT.
• Septic pulmonary emboli visualized on chest x-ray, a complication that occurred in 64% of the dual diagnosis group versus just 1% of patients with DVT without AHO.
• A band percentage of white blood cells greater than 1.5%, present in 86% of children with AHO and DVT.

More than 90% of children with AHO and DVT underwent surgery, with a mean of 2.7 surgeries per child, in contrast to the group with AHO without DVT, 55% of whom had surgery, with a mean of 0.7 surgeries per child.

Of note, there was no significant difference in the occurrence of pulmonary embolism between children with DVT without AHO versus those with DVT and AHO, with a rate of about 10% in both groups.

Dr. Copley reported having no relevant financial conflicts.

bjancin@mdedge.com

MALMO, SWEDEN – Early identification of deep vein thrombosis in children with acute hematogenous osteomyelitis is critical given the need to plan anticoagulation management around the high likelihood that such patients will undergo multiple surgeries, Lawson A.B. Copley, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

He and his coinvestigators have identified a handful of risk factors helpful in expediting recognition of deep vein thrombosis (DVT) in children with suspected invasive infection of the musculoskeletal system.

“To improve the rate and timing of identification of DVT, we recommend performing early screening ultrasound on all children with these risk factors who are suspected of having acute hematogenous osteomyelitis,” declared Dr. Copley, professor of orthopaedic surgery and pediatrics at the University of Texas, Dallas.

Delayed diagnosis of DVT in the setting of acute hematogenous osteomyelitis (AHO) is common. Indeed, in a review of the experience at Children’s Medical Center Dallas during 2012-2014, the average time delay from ICU admission in patients suspected of having AHO to identification of DVT by ultrasound was 6.3 days.

“We’ve changed some things on the basis of that study in order to accelerate that timeline,” he explained.

Their major change was to identify actionable risk factors for DVT. This was accomplished by conducting a retrospective study of the EHR of nearly 902,000 Texas children during 2008-2016.

The study demonstrated that children with AHO complicated by DVT are, from the get-go, very different from AHO patients without DVT. They have higher illness severity of illness, are more likely to be admitted to the ICU, are prone to methicillin-resistant Staphylococcus aureus infection with prolonged bacteremia, and are much more likely to undergo multiple surgeries. Moreover, children with AHO and DVT differed substantially from other children with DVT: The dual diagnosis children lacked comorbid conditions, were prone to septic pulmonary emboli, didn’t develop postthrombotic syndrome marked by chronic venous stasis and ulcerations, and had invariably negative coagulopathy workups.

“There is no need, we feel, to perform a hypercoagulopathy workup in children with AHO complicated by DVT,” Dr. Copley said.

Drilling deeper into the data, he and his coinvestigators identified 224 new cases of DVT in the study population, for a prevalence of 2.5 per 10,000 children, along with 466 children with AHO. A total of 6% of children with AHO had DVT, and 12.1% of all children with DVT had AHO. The researchers then compared the demographics, laboratory parameters, and treatment in three cohorts: the 196 children with DVT without AHO, 28 with both AHO and DVT, and 438 with AHO without DVT.

Through this analysis, they came up with a list of risk factors warranting early screening ultrasound in children suspected of having AHO:

• An initial C-reactive protein level above 8 mg/dL, which was present in all 28 dual diagnosis children.
• ICU admission, which occurred in 19 of 28 (68%) children.
• A severity of illness score of at least 7 on a 10-point scale during the first several days in the hospital, present in 27 of the 28 children. The severity of illness scale was developed and validated by Dr. Copley and coworkers (J Pediatr Orthop. 2016 Oct 12. doi: 10.1097/BPO.0000000000000879).
• Bacteremia in the initial blood culture, present in 23 of 28 patients (82%).
• Just under 90% of the children with AHO and DVT had methicillin-resistant S. aureus, compared with 20% of those with AHO without DVT.
• Septic pulmonary emboli visualized on chest x-ray, a complication that occurred in 64% of the dual diagnosis group versus just 1% of patients with DVT without AHO.
• A band percentage of white blood cells greater than 1.5%, present in 86% of children with AHO and DVT.

More than 90% of children with AHO and DVT underwent surgery, with a mean of 2.7 surgeries per child, in contrast to the group with AHO without DVT, 55% of whom had surgery, with a mean of 0.7 surgeries per child.

Of note, there was no significant difference in the occurrence of pulmonary embolism between children with DVT without AHO versus those with DVT and AHO, with a rate of about 10% in both groups.

Dr. Copley reported having no relevant financial conflicts.

bjancin@mdedge.com

© Universitätsklinikum Freiburg

New research suggests dasatinib could treat certain patients with juvenile myelomonocytic leukemia (JMML) or acute myeloid leukemia (AML).

The study showed that TNK2 inhibition has a negative effect on PTPN11-mutant leukemias.

PTPN11-mutant JMML and AML cells were sensitive to treatment with dasatinib, which inhibits TNK2.

Dasatinib also induced hematologic remission in a patient with PTPN11-mutant JMML.

Investigators reported these results in Science Signaling.

Past research showed that mutations in PTPN11 result in excessive cell proliferation and drive tumor growth in some cases of JMML and AML.

In the current study, investigators analyzed PTPN11-mutated leukemia cells and found that PTPN11 is activated by TNK2.

The investigators said TNK2 phosphorylates PTPN11, which then dephosphorylates TNK2 in a negative feedback loop. They also found that coexpression of TNK2 and mutant PTPN11 results in “robust” MAPK pathway activation.

Inhibiting TNK2 with dasatinib blocked MAPK signaling and colony formation in vitro.

Additional experiments showed that PTPN11-mutant AML samples were significantly more sensitive to dasatinib than wild-type AML samples.

Investigators also tested dasatinib in a sample from a JMML patient carrying a PTPN11 G60R mutation.

This patient’s cells were 10 times more sensitive to dasatinib than the average sample from a cohort of 151 patients who had AML, acute lymphoblastic leukemia, myeloproliferative neoplasms, or chronic lymphocytic leukemia.

Because the JMML patient’s cells were so responsive to dasatinib, the investigators decided to administer the drug to the patient.

The patient achieved sustained hematologic remission with dasatinib, and this allowed him to receive a stem cell transplant using an unrelated cord blood donor. The patient had previously failed 2 transplants (with myeloablative conditioning) from a matched sibling donor.

The third transplant prolonged the patient’s life by a year, but he eventually died of relapsed disease.

The investigators said this case study and the in vitro results support further investigation into the efficacy of dasatinib and other TNK2 inhibitors in PTPN11-mutant leukemias.

© Universitätsklinikum Freiburg

New research suggests dasatinib could treat certain patients with juvenile myelomonocytic leukemia (JMML) or acute myeloid leukemia (AML).

The study showed that TNK2 inhibition has a negative effect on PTPN11-mutant leukemias.

PTPN11-mutant JMML and AML cells were sensitive to treatment with dasatinib, which inhibits TNK2.

Dasatinib also induced hematologic remission in a patient with PTPN11-mutant JMML.

Investigators reported these results in Science Signaling.

Past research showed that mutations in PTPN11 result in excessive cell proliferation and drive tumor growth in some cases of JMML and AML.

In the current study, investigators analyzed PTPN11-mutated leukemia cells and found that PTPN11 is activated by TNK2.

The investigators said TNK2 phosphorylates PTPN11, which then dephosphorylates TNK2 in a negative feedback loop. They also found that coexpression of TNK2 and mutant PTPN11 results in “robust” MAPK pathway activation.

Inhibiting TNK2 with dasatinib blocked MAPK signaling and colony formation in vitro.

Additional experiments showed that PTPN11-mutant AML samples were significantly more sensitive to dasatinib than wild-type AML samples.

Investigators also tested dasatinib in a sample from a JMML patient carrying a PTPN11 G60R mutation.

This patient’s cells were 10 times more sensitive to dasatinib than the average sample from a cohort of 151 patients who had AML, acute lymphoblastic leukemia, myeloproliferative neoplasms, or chronic lymphocytic leukemia.

Because the JMML patient’s cells were so responsive to dasatinib, the investigators decided to administer the drug to the patient.

The patient achieved sustained hematologic remission with dasatinib, and this allowed him to receive a stem cell transplant using an unrelated cord blood donor. The patient had previously failed 2 transplants (with myeloablative conditioning) from a matched sibling donor.

The third transplant prolonged the patient’s life by a year, but he eventually died of relapsed disease.

The investigators said this case study and the in vitro results support further investigation into the efficacy of dasatinib and other TNK2 inhibitors in PTPN11-mutant leukemias.

© Universitätsklinikum Freiburg

New research suggests dasatinib could treat certain patients with juvenile myelomonocytic leukemia (JMML) or acute myeloid leukemia (AML).

The study showed that TNK2 inhibition has a negative effect on PTPN11-mutant leukemias.

PTPN11-mutant JMML and AML cells were sensitive to treatment with dasatinib, which inhibits TNK2.

Dasatinib also induced hematologic remission in a patient with PTPN11-mutant JMML.

Investigators reported these results in Science Signaling.

Past research showed that mutations in PTPN11 result in excessive cell proliferation and drive tumor growth in some cases of JMML and AML.

In the current study, investigators analyzed PTPN11-mutated leukemia cells and found that PTPN11 is activated by TNK2.

The investigators said TNK2 phosphorylates PTPN11, which then dephosphorylates TNK2 in a negative feedback loop. They also found that coexpression of TNK2 and mutant PTPN11 results in “robust” MAPK pathway activation.

Inhibiting TNK2 with dasatinib blocked MAPK signaling and colony formation in vitro.

Additional experiments showed that PTPN11-mutant AML samples were significantly more sensitive to dasatinib than wild-type AML samples.

Investigators also tested dasatinib in a sample from a JMML patient carrying a PTPN11 G60R mutation.

This patient’s cells were 10 times more sensitive to dasatinib than the average sample from a cohort of 151 patients who had AML, acute lymphoblastic leukemia, myeloproliferative neoplasms, or chronic lymphocytic leukemia.

Because the JMML patient’s cells were so responsive to dasatinib, the investigators decided to administer the drug to the patient.

The patient achieved sustained hematologic remission with dasatinib, and this allowed him to receive a stem cell transplant using an unrelated cord blood donor. The patient had previously failed 2 transplants (with myeloablative conditioning) from a matched sibling donor.

The third transplant prolonged the patient’s life by a year, but he eventually died of relapsed disease.

The investigators said this case study and the in vitro results support further investigation into the efficacy of dasatinib and other TNK2 inhibitors in PTPN11-mutant leukemias.

Adolescents who frequently used digital media were more likely to develop subsequent symptoms of ADHD over a 2 year period, according to results from a prospective, longitudinal cohort study published in JAMA.

monkeybusinessimages/iStock/Getty Images Plus

“Further research is needed to determine whether this association is causal,” cautioned the investigators.

Between fall 2014 (10th grade) and fall 2016 (12th grade), researchers studied 3,051 students from 10 different Los Angeles schools who were enrolled in the Happiness & Health Study and did not have significant ADHD symptoms; of these students, 2,587 adolescents (mean age 16 years, 54% girls) self-reported digital media use activities from 14 different types through surveys administered at baseline and again at 6-month, 12-month, 18-month and 24-month follow-up. Digital use activities included checking social media sites, engaging with social media content, texting, streaming music, and browsing or viewing images or videos, among others.

“Although some emerging research indicates that ADHD levels and use of certain forms of modern media may be concurrently associated, the role of modern digital media use in ADHD risk largely remains unclear from the prior literature due to limitations in exposure assessment and the application of designs incapable of supporting temporal or causal inferences,” wrote Chaelin K. Ra, MPH, of the University of Southern California, Los Angeles, and his colleagues. “The current study provides new longitudinal evidence on this topic using a 5-wave prospective design and comprehensive assessment across a wide continuum of digital media exposure, including numerous media platforms currently popular among youth.”

Students ranked their activities in a cumulative index and indicated whether they participated in those activities “0, 1-2 times per week, 1-2 times per day, or many times per day.” They also filled out the DSM-IV Current Symptoms Self-Report Form, which asked them to report whether they experienced any of nine different hyperactivity-impulsivity symptoms such as “difficulty organizing and completing tasks.”

Mr. Ra and his colleagues found that 81% of adolescents reported at least one digital media activity performed at a high-frequency rate, with 54% reporting they checked social media at a high-frequency rate. There was a mean of four baseline digital media activities performed at a high-frequency rate among students surveyed. Each additional digital media activity used at a high-frequency rate carried a statistically significant association of subsequent ADHD symptoms over the follow-up period (odds ratio 1.1; 95% confidence interval, 1.06-1.16), which remained after adjustment for covariates including age, sex, and subsidized lunch availability tied to family income (OR 1.1; 95% CI, 1.05-1.15). The researchers noted that there was a 5% mean prevalence of subsequent ADHD symptoms in follow-up among patients who reported no baseline high-frequency rate of digital media use, compared with 10% in students indicating 7 high-frequency activities and 11% in students indicating 14 high-frequency activities.

Limitations of the study included potential inaccuracies in self-reporting ADHD symptoms as opposed to students receiving a diagnosis through a clinical interview, the possibility of the association being influenced by ADHD symptoms not detected in the study, the fact that the media use measure in the study had not been validated, and use of a targeted age range in the sample of students that excluded students without surveys who had differing demographic data from the rest of the cohort, according to the researchers.

The authors reported having no relevant financial disclosures. The study was supported by a grant from the National Institutes of Health.

SOURCE: Ra CK et al. JAMA. 2018 Jul 17. doi: 10.1001/jama.2018.8931.

Adolescents who frequently used digital media were more likely to develop subsequent symptoms of ADHD over a 2 year period, according to results from a prospective, longitudinal cohort study published in JAMA.

monkeybusinessimages/iStock/Getty Images Plus

“Further research is needed to determine whether this association is causal,” cautioned the investigators.

Between fall 2014 (10th grade) and fall 2016 (12th grade), researchers studied 3,051 students from 10 different Los Angeles schools who were enrolled in the Happiness & Health Study and did not have significant ADHD symptoms; of these students, 2,587 adolescents (mean age 16 years, 54% girls) self-reported digital media use activities from 14 different types through surveys administered at baseline and again at 6-month, 12-month, 18-month and 24-month follow-up. Digital use activities included checking social media sites, engaging with social media content, texting, streaming music, and browsing or viewing images or videos, among others.

“Although some emerging research indicates that ADHD levels and use of certain forms of modern media may be concurrently associated, the role of modern digital media use in ADHD risk largely remains unclear from the prior literature due to limitations in exposure assessment and the application of designs incapable of supporting temporal or causal inferences,” wrote Chaelin K. Ra, MPH, of the University of Southern California, Los Angeles, and his colleagues. “The current study provides new longitudinal evidence on this topic using a 5-wave prospective design and comprehensive assessment across a wide continuum of digital media exposure, including numerous media platforms currently popular among youth.”

Students ranked their activities in a cumulative index and indicated whether they participated in those activities “0, 1-2 times per week, 1-2 times per day, or many times per day.” They also filled out the DSM-IV Current Symptoms Self-Report Form, which asked them to report whether they experienced any of nine different hyperactivity-impulsivity symptoms such as “difficulty organizing and completing tasks.”

Mr. Ra and his colleagues found that 81% of adolescents reported at least one digital media activity performed at a high-frequency rate, with 54% reporting they checked social media at a high-frequency rate. There was a mean of four baseline digital media activities performed at a high-frequency rate among students surveyed. Each additional digital media activity used at a high-frequency rate carried a statistically significant association of subsequent ADHD symptoms over the follow-up period (odds ratio 1.1; 95% confidence interval, 1.06-1.16), which remained after adjustment for covariates including age, sex, and subsidized lunch availability tied to family income (OR 1.1; 95% CI, 1.05-1.15). The researchers noted that there was a 5% mean prevalence of subsequent ADHD symptoms in follow-up among patients who reported no baseline high-frequency rate of digital media use, compared with 10% in students indicating 7 high-frequency activities and 11% in students indicating 14 high-frequency activities.

Limitations of the study included potential inaccuracies in self-reporting ADHD symptoms as opposed to students receiving a diagnosis through a clinical interview, the possibility of the association being influenced by ADHD symptoms not detected in the study, the fact that the media use measure in the study had not been validated, and use of a targeted age range in the sample of students that excluded students without surveys who had differing demographic data from the rest of the cohort, according to the researchers.

The authors reported having no relevant financial disclosures. The study was supported by a grant from the National Institutes of Health.

SOURCE: Ra CK et al. JAMA. 2018 Jul 17. doi: 10.1001/jama.2018.8931.

Adolescents who frequently used digital media were more likely to develop subsequent symptoms of ADHD over a 2 year period, according to results from a prospective, longitudinal cohort study published in JAMA.

monkeybusinessimages/iStock/Getty Images Plus

“Further research is needed to determine whether this association is causal,” cautioned the investigators.

Between fall 2014 (10th grade) and fall 2016 (12th grade), researchers studied 3,051 students from 10 different Los Angeles schools who were enrolled in the Happiness & Health Study and did not have significant ADHD symptoms; of these students, 2,587 adolescents (mean age 16 years, 54% girls) self-reported digital media use activities from 14 different types through surveys administered at baseline and again at 6-month, 12-month, 18-month and 24-month follow-up. Digital use activities included checking social media sites, engaging with social media content, texting, streaming music, and browsing or viewing images or videos, among others.

“Although some emerging research indicates that ADHD levels and use of certain forms of modern media may be concurrently associated, the role of modern digital media use in ADHD risk largely remains unclear from the prior literature due to limitations in exposure assessment and the application of designs incapable of supporting temporal or causal inferences,” wrote Chaelin K. Ra, MPH, of the University of Southern California, Los Angeles, and his colleagues. “The current study provides new longitudinal evidence on this topic using a 5-wave prospective design and comprehensive assessment across a wide continuum of digital media exposure, including numerous media platforms currently popular among youth.”

Students ranked their activities in a cumulative index and indicated whether they participated in those activities “0, 1-2 times per week, 1-2 times per day, or many times per day.” They also filled out the DSM-IV Current Symptoms Self-Report Form, which asked them to report whether they experienced any of nine different hyperactivity-impulsivity symptoms such as “difficulty organizing and completing tasks.”

Mr. Ra and his colleagues found that 81% of adolescents reported at least one digital media activity performed at a high-frequency rate, with 54% reporting they checked social media at a high-frequency rate. There was a mean of four baseline digital media activities performed at a high-frequency rate among students surveyed. Each additional digital media activity used at a high-frequency rate carried a statistically significant association of subsequent ADHD symptoms over the follow-up period (odds ratio 1.1; 95% confidence interval, 1.06-1.16), which remained after adjustment for covariates including age, sex, and subsidized lunch availability tied to family income (OR 1.1; 95% CI, 1.05-1.15). The researchers noted that there was a 5% mean prevalence of subsequent ADHD symptoms in follow-up among patients who reported no baseline high-frequency rate of digital media use, compared with 10% in students indicating 7 high-frequency activities and 11% in students indicating 14 high-frequency activities.

Limitations of the study included potential inaccuracies in self-reporting ADHD symptoms as opposed to students receiving a diagnosis through a clinical interview, the possibility of the association being influenced by ADHD symptoms not detected in the study, the fact that the media use measure in the study had not been validated, and use of a targeted age range in the sample of students that excluded students without surveys who had differing demographic data from the rest of the cohort, according to the researchers.

The authors reported having no relevant financial disclosures. The study was supported by a grant from the National Institutes of Health.

SOURCE: Ra CK et al. JAMA. 2018 Jul 17. doi: 10.1001/jama.2018.8931.

Nearly three-quarters of opioid-related adverse events seen in children were related to therapeutic opioid use, based on data from more than a million prescriptions.

BackyardProduction/Thinkstock

Prescription of opioids to children for outpatient conditions may have risen along with the increased opioid prescriptions for adults, but most of the literature focuses on opioid toxicity in children, and “the incidence of adverse opioid effects for children during appropriate medical use for relatively minor conditions is unknown,” wrote Cecilia P. Chung, MD, of Vanderbilt University in Nashville, Tenn., and her colleagues.

In a retrospective study published in Pediatrics, the researchers reviewed data from 401,972 children and adolescents aged 2-17 years with no chronic or severe conditions. The patients filled a total of 1,362,503 prescriptions for opioids, with a mean 15% filling one or more opioid prescriptions a year, and 1 in every 2,611 prescriptions was followed by an emergency department visit, hospitalization, or death related to an adverse event associated with opioid use.

Approximately 20% of the prescriptions were for children aged 2-5 years, 28% for ages 6-11 years, and 52% for ages 12-17 years. The patients were enrolled in Medicaid between Jan. 1, 1999, and Dec. 31, 2014, in Tennessee, and were seen at outpatient centers. Dental procedures were the most common reasons for opioid prescriptions in the study population (31%), followed by outpatient procedures or surgeries (25%), trauma (18%), and infections (16%).

Overall, 437 cases of opioid-related adverse events were confirmed by medical record review; 89% of these were deemed related to the prescription, and 71% were related to proper therapeutic use, the researchers said. The remainder were considered to be related to unintentional overdose, abuse, self-harm, or the circumstances were not indicated.

The opioid-related symptoms most frequently were gastrointestinal, neuropsychiatric, dermatologic, and central nervous system depression.

“The incidence of opioid-related adverse events increased for children and adolescents 12-17 years of age, during current opioid use, and with higher opioid doses,” the researchers said.

The study findings were limited by several factors including the use of Medicaid patients only, the lack of clinical details such as patient weight, and the potential for incomplete medical records, Dr. Chung and her associates noted. However, the results support the need for more comprehensive guidelines in treating acute, self-limited conditions in children to reduce unnecessary opioid exposure, they said.

The researchers had no relevant financial conflicts to disclose. The study was supported by the Eunice Kennedy Shriver National Institute for Child Health and Human Development and funded by the National Institutes of Health. Dr. Chung received grant support from the National Institutes of Health and the Rheumatology Research Foundation Career Development Research K-supplement.

SOURCE: Chung C et al. Pediatrics. 2018 Jul 16. doi: 10.1542/peds.2017-2156.

Nearly three-quarters of opioid-related adverse events seen in children were related to therapeutic opioid use, based on data from more than a million prescriptions.

BackyardProduction/Thinkstock

Prescription of opioids to children for outpatient conditions may have risen along with the increased opioid prescriptions for adults, but most of the literature focuses on opioid toxicity in children, and “the incidence of adverse opioid effects for children during appropriate medical use for relatively minor conditions is unknown,” wrote Cecilia P. Chung, MD, of Vanderbilt University in Nashville, Tenn., and her colleagues.

In a retrospective study published in Pediatrics, the researchers reviewed data from 401,972 children and adolescents aged 2-17 years with no chronic or severe conditions. The patients filled a total of 1,362,503 prescriptions for opioids, with a mean 15% filling one or more opioid prescriptions a year, and 1 in every 2,611 prescriptions was followed by an emergency department visit, hospitalization, or death related to an adverse event associated with opioid use.

Approximately 20% of the prescriptions were for children aged 2-5 years, 28% for ages 6-11 years, and 52% for ages 12-17 years. The patients were enrolled in Medicaid between Jan. 1, 1999, and Dec. 31, 2014, in Tennessee, and were seen at outpatient centers. Dental procedures were the most common reasons for opioid prescriptions in the study population (31%), followed by outpatient procedures or surgeries (25%), trauma (18%), and infections (16%).

Overall, 437 cases of opioid-related adverse events were confirmed by medical record review; 89% of these were deemed related to the prescription, and 71% were related to proper therapeutic use, the researchers said. The remainder were considered to be related to unintentional overdose, abuse, self-harm, or the circumstances were not indicated.

The opioid-related symptoms most frequently were gastrointestinal, neuropsychiatric, dermatologic, and central nervous system depression.

“The incidence of opioid-related adverse events increased for children and adolescents 12-17 years of age, during current opioid use, and with higher opioid doses,” the researchers said.

The study findings were limited by several factors including the use of Medicaid patients only, the lack of clinical details such as patient weight, and the potential for incomplete medical records, Dr. Chung and her associates noted. However, the results support the need for more comprehensive guidelines in treating acute, self-limited conditions in children to reduce unnecessary opioid exposure, they said.

The researchers had no relevant financial conflicts to disclose. The study was supported by the Eunice Kennedy Shriver National Institute for Child Health and Human Development and funded by the National Institutes of Health. Dr. Chung received grant support from the National Institutes of Health and the Rheumatology Research Foundation Career Development Research K-supplement.

SOURCE: Chung C et al. Pediatrics. 2018 Jul 16. doi: 10.1542/peds.2017-2156.

Nearly three-quarters of opioid-related adverse events seen in children were related to therapeutic opioid use, based on data from more than a million prescriptions.

BackyardProduction/Thinkstock

Prescription of opioids to children for outpatient conditions may have risen along with the increased opioid prescriptions for adults, but most of the literature focuses on opioid toxicity in children, and “the incidence of adverse opioid effects for children during appropriate medical use for relatively minor conditions is unknown,” wrote Cecilia P. Chung, MD, of Vanderbilt University in Nashville, Tenn., and her colleagues.

In a retrospective study published in Pediatrics, the researchers reviewed data from 401,972 children and adolescents aged 2-17 years with no chronic or severe conditions. The patients filled a total of 1,362,503 prescriptions for opioids, with a mean 15% filling one or more opioid prescriptions a year, and 1 in every 2,611 prescriptions was followed by an emergency department visit, hospitalization, or death related to an adverse event associated with opioid use.

Approximately 20% of the prescriptions were for children aged 2-5 years, 28% for ages 6-11 years, and 52% for ages 12-17 years. The patients were enrolled in Medicaid between Jan. 1, 1999, and Dec. 31, 2014, in Tennessee, and were seen at outpatient centers. Dental procedures were the most common reasons for opioid prescriptions in the study population (31%), followed by outpatient procedures or surgeries (25%), trauma (18%), and infections (16%).

Overall, 437 cases of opioid-related adverse events were confirmed by medical record review; 89% of these were deemed related to the prescription, and 71% were related to proper therapeutic use, the researchers said. The remainder were considered to be related to unintentional overdose, abuse, self-harm, or the circumstances were not indicated.

The opioid-related symptoms most frequently were gastrointestinal, neuropsychiatric, dermatologic, and central nervous system depression.

“The incidence of opioid-related adverse events increased for children and adolescents 12-17 years of age, during current opioid use, and with higher opioid doses,” the researchers said.

The study findings were limited by several factors including the use of Medicaid patients only, the lack of clinical details such as patient weight, and the potential for incomplete medical records, Dr. Chung and her associates noted. However, the results support the need for more comprehensive guidelines in treating acute, self-limited conditions in children to reduce unnecessary opioid exposure, they said.

The researchers had no relevant financial conflicts to disclose. The study was supported by the Eunice Kennedy Shriver National Institute for Child Health and Human Development and funded by the National Institutes of Health. Dr. Chung received grant support from the National Institutes of Health and the Rheumatology Research Foundation Career Development Research K-supplement.

SOURCE: Chung C et al. Pediatrics. 2018 Jul 16. doi: 10.1542/peds.2017-2156.

TORONTO – Febrile infants were less likely to undergo invasive diagnostic testing at community hospitals versus university-affiliated ones, but had similar outcomes, according to a study presented at the Pediatric Academic Societies annual meeting.

“The community hospitals are doing less procedures on the infants, but with basically the exact same outcomes,” said Beth C. Natt, MD, MPH, director of pediatric hospital medicine at Bridgeport (Conn.) Hospital.

Babies who presented to university-affiliated hospitals were more likely to be hospitalized (70% vs. 67%; P = .001) than were those at community hospitals, but had a similar likelihood of being diagnosed with bacteremia, meningitis, or urinary tract infection. The rates of missed bacterial infection were 0.8% for teaching hospitals and 1% for community hospitals (P = .346).

“There is some thought that in community settings, because we’re not completing the workup in the standard, protocolized way seen at teaching hospitals, we might be doing wrong by the children, but these data show we’re actually doing just fine,” Dr. Natt said in an interview.

She and her colleagues reviewed 9,884 febrile infant evaluations occurring at 132 hospitals participating in the Reducing Excessive Variation in the Infant Sepsis Evaluation (REVISE) quality improvement project. Two-thirds of the infants (n = 6,479) were evaluated across 78 university-affiliated hospitals and 3,405 (or 34%) were seen at 54 community hospitals. Hospital status was self-reported.

The teaching hospitals more often had at least one pediatric emergency medicine provider, compared with community hospitals (90% vs. 57%; P = .001) and were more likely to see babies between 7 and 30 days old (90% vs. 57%; P = .001). They also were more likely to obtain urine cultures (92% vs. 88%; P = 0.001), blood cultures (84% vs. 80%; P = .001), and cerebral spinal fluid cultures (62% vs. 57%; P = .001).

On the other hand, community hospitals were significantly more likely to see children presenting with respiratory symptoms (39% vs. 36% for teaching hospitals; P = .014), and were more likely to order chest x-rays on febrile infants (32% vs. 24% for university-affiliated hospitals; P = .001).

“As a community hospitalist, the results weren’t that surprising to me,” said Dr. Natt. “If anything was surprising it was how often we were doing chest x-rays, but I think that had to do with the fact that we had more children with respiratory symptoms coming to community hospitals.

“The American Academy of Pediatrics guidelines for fever were written last in 1993, when I was in high school, so they are very due to be revised,” said Dr. Natt. “I suspect the new guidelines will have us doing fewer spinal taps in children and more watchful waiting.”

TORONTO – Febrile infants were less likely to undergo invasive diagnostic testing at community hospitals versus university-affiliated ones, but had similar outcomes, according to a study presented at the Pediatric Academic Societies annual meeting.

“The community hospitals are doing less procedures on the infants, but with basically the exact same outcomes,” said Beth C. Natt, MD, MPH, director of pediatric hospital medicine at Bridgeport (Conn.) Hospital.

Babies who presented to university-affiliated hospitals were more likely to be hospitalized (70% vs. 67%; P = .001) than were those at community hospitals, but had a similar likelihood of being diagnosed with bacteremia, meningitis, or urinary tract infection. The rates of missed bacterial infection were 0.8% for teaching hospitals and 1% for community hospitals (P = .346).

“There is some thought that in community settings, because we’re not completing the workup in the standard, protocolized way seen at teaching hospitals, we might be doing wrong by the children, but these data show we’re actually doing just fine,” Dr. Natt said in an interview.

She and her colleagues reviewed 9,884 febrile infant evaluations occurring at 132 hospitals participating in the Reducing Excessive Variation in the Infant Sepsis Evaluation (REVISE) quality improvement project. Two-thirds of the infants (n = 6,479) were evaluated across 78 university-affiliated hospitals and 3,405 (or 34%) were seen at 54 community hospitals. Hospital status was self-reported.

The teaching hospitals more often had at least one pediatric emergency medicine provider, compared with community hospitals (90% vs. 57%; P = .001) and were more likely to see babies between 7 and 30 days old (90% vs. 57%; P = .001). They also were more likely to obtain urine cultures (92% vs. 88%; P = 0.001), blood cultures (84% vs. 80%; P = .001), and cerebral spinal fluid cultures (62% vs. 57%; P = .001).

On the other hand, community hospitals were significantly more likely to see children presenting with respiratory symptoms (39% vs. 36% for teaching hospitals; P = .014), and were more likely to order chest x-rays on febrile infants (32% vs. 24% for university-affiliated hospitals; P = .001).

“As a community hospitalist, the results weren’t that surprising to me,” said Dr. Natt. “If anything was surprising it was how often we were doing chest x-rays, but I think that had to do with the fact that we had more children with respiratory symptoms coming to community hospitals.

“The American Academy of Pediatrics guidelines for fever were written last in 1993, when I was in high school, so they are very due to be revised,” said Dr. Natt. “I suspect the new guidelines will have us doing fewer spinal taps in children and more watchful waiting.”

TORONTO – Febrile infants were less likely to undergo invasive diagnostic testing at community hospitals versus university-affiliated ones, but had similar outcomes, according to a study presented at the Pediatric Academic Societies annual meeting.

“The community hospitals are doing less procedures on the infants, but with basically the exact same outcomes,” said Beth C. Natt, MD, MPH, director of pediatric hospital medicine at Bridgeport (Conn.) Hospital.

Babies who presented to university-affiliated hospitals were more likely to be hospitalized (70% vs. 67%; P = .001) than were those at community hospitals, but had a similar likelihood of being diagnosed with bacteremia, meningitis, or urinary tract infection. The rates of missed bacterial infection were 0.8% for teaching hospitals and 1% for community hospitals (P = .346).

“There is some thought that in community settings, because we’re not completing the workup in the standard, protocolized way seen at teaching hospitals, we might be doing wrong by the children, but these data show we’re actually doing just fine,” Dr. Natt said in an interview.

She and her colleagues reviewed 9,884 febrile infant evaluations occurring at 132 hospitals participating in the Reducing Excessive Variation in the Infant Sepsis Evaluation (REVISE) quality improvement project. Two-thirds of the infants (n = 6,479) were evaluated across 78 university-affiliated hospitals and 3,405 (or 34%) were seen at 54 community hospitals. Hospital status was self-reported.

The teaching hospitals more often had at least one pediatric emergency medicine provider, compared with community hospitals (90% vs. 57%; P = .001) and were more likely to see babies between 7 and 30 days old (90% vs. 57%; P = .001). They also were more likely to obtain urine cultures (92% vs. 88%; P = 0.001), blood cultures (84% vs. 80%; P = .001), and cerebral spinal fluid cultures (62% vs. 57%; P = .001).

On the other hand, community hospitals were significantly more likely to see children presenting with respiratory symptoms (39% vs. 36% for teaching hospitals; P = .014), and were more likely to order chest x-rays on febrile infants (32% vs. 24% for university-affiliated hospitals; P = .001).

“As a community hospitalist, the results weren’t that surprising to me,” said Dr. Natt. “If anything was surprising it was how often we were doing chest x-rays, but I think that had to do with the fact that we had more children with respiratory symptoms coming to community hospitals.

“The American Academy of Pediatrics guidelines for fever were written last in 1993, when I was in high school, so they are very due to be revised,” said Dr. Natt. “I suspect the new guidelines will have us doing fewer spinal taps in children and more watchful waiting.”