Concussion Recommendations in Children and Adolescents in Sports Related Injuries

In recent years, concussions have made their way into the media more and more. Something that we once thought was a simple injury that could be shaken off is now being thought of as a serious injury.  There are specialists who dedicate their practice to concussions.  This type of injury is commonly associated with sports.  Concussions are a common injury that occurs in sports especially football.  It has been somewhat of a controversy this past decade because the NFL has made changes in their roles and regulations to protect the players from concussion injuries.  Children and adolescents are also affected from these injuries.  This article looked at how providers are supposed to handle young patients that have sustained a head injury.

Within 1 to 2 days of the injury, the patient should be presented to a physical to have symptoms checked.  The patient should not be left unattended within 48 hours of the injury.  Rest for the first 1 to 2 days is critical to the patient’s recovery.  It is not, however, recommended for the patient to have prolonged bed rest.  The notion that patients should rest until there are no longer any symptoms is not the preferred method of treatment anymore.  Patients should return to school and normal activity within a couple weeks to avoid depression and other negative symptoms.  Accommodations can be made but can usually be discontinued within 2 weeks.

A system was developed called SAFE (Symptoms, Assessment, Follow-up, Execute, and return to pay) to help providers decide what actions need to be taken with the patient.  This system was made into a flow chart so that a provider can follow the protocol for each patient.  This system can help determine when a patient should be referred to a specialist and what kind of tests need to be performed.  It also helps figure out back to school and return to play times.  There have been laws passed in all 50 states to help outline when a patient is ok to come to back and play for their sport.  This article shows how important it is to have a standard method of treatment for patients with concussions.  Each patient may be different, but this method could help make sure that the provider is doing their best to follows the protocol treatment for each patient.

ORTHOPEDICS. 2016; 39: 24-30

http://ORTHOPEDICS. 2016; 39: 24-30

Acetaminophen administration in pediatric age: an observational prospective cross-sectional study

Fever phobia is a phenomenon seem among parents who think fever is a health danger instead of an important physiological response and mechanism of defense against infection. Because of this parents tend to increase self medication which results in inappropriate use of antipyretics, and most commonly acetaminophen. The issue also comes from the fact that acetaminophen is dosed in children according to weight and not age, so the wrong measurement or guess of a child’s weight leads misdosing. The appropriate dosage is 10-15 mg/kg/dose every 4-6 hours, and higher or more frequent doses can cause hepatotoxicity which is why correct dosing is so important.

For six months, from November 2012 to April 2013, an observational cross-sectional study was performed to evaluate the dosage of acetaminophen administered to children with fever as mg/kg/dose and as a total daily quantity in mg/kg/day and to identify factors that may influences the accuracy of dosing. The clinical records of 1,397 children who had an outpatient visit due to fever between the ages of 1 month to 16 years old were examined. 74% of those children were given acetaminophen and had a body temperature below 38.4°C (or 101.12°F) which is justified because of the attempt to reduce the discomfort of the fever. Dosages up to 15 mg/kg/dose and a daily quantity of <90 mg/kg/day was considered normal and not potentially dangerous. And dosages of >15 mg/kg/dose and >90 mg/kg/day was considered supratherapuetic and potentially dangerous.

The results of the study were that in 1,060 cases, <90 mg/kg/day dose of acetaminophen was administered, and in 337 cases, >90 mg/kg/day dose of acetaminophen were administered. The researchers discovered that higher daily doses of acetaminophen were administered be caregivers with higher levels of education with 71% having a university degree within the >90 mg/kg/day dosing, in comparison to the <90 mg/kg/day group having 63% of the caregivers having secondary education. In addition acetaminophen doses were significantly higher in those who were given drops or syrups than those who were given tablets or suppositories. And a higher risk of acetaminophen overdose was seen when drops and or syrup formula were used. Moreover, 85.7% of the children had a acetaminophen prescription be a health professional, but even then 9.82% of acetaminophen overdose was found.

Although this study was done overseas in Italy and not in America, this is still a prevalent and important issue for pharmacists to be aware of. If we become aware this is an issues, then whenever parents are coming in to pick up acetaminophen prescriptions we can make sure to double check that the dosing is appropriate for the weight of the children to prevent this issue from occurring and to prevent any chances of hepatotoxicity from happening in children too. Not only that but other health care providers like the doctors play a role too, if we can educate them and make them aware of this issue then the right prescription dosages can be written further preventing acetaminophen overdose.

Lubrano R, Paoli S, Bonci M, et al. Acetaminophen administration in pediatric age: an observational prospective cross-sectional study. Ital J Pediatr. 2016;42:20.

Routine Amoxicillin for Uncomplicated Severe Acute Malnutrition in Children

Approximately 19 million children under the age of 5 worldwide suffer from severe acute malnutrition. This condition contributes greatly to mortality and disease burden among children. In order to reduce the risk of death from severe acute malnutrition, nutritional and medical intervention is required. Furthermore, bacterial infection can complicate cases of severe acute malnutrition, since the risk of infection is high. For this reason, in 1999 the World Health Organization (WHO) recommended the routine use of broad spectrum antibiotics for the management of severe acute malnutrition. More recent statistics show that malnutrition is 4 to 5 times as high as the number before the introduction of standards of treatment. Despite the recent developments, there has been no strong evidence about whether the use of the same medical protocol for community based regimens should be used. Thus, researchers conducted a randomized, double-blind, placebo-controlled trial in Niger to examine the effect of routine amoxicillin use on nutritional recovery in children with severe acute malnutrition.

Overall, 64% of the children enrolled in the study recovered from severe acute malnutrition. However, these results did not significantly indicate that routine provision of amoxicillin was superior to placebo for nutritional recovery in children with uncomplicated severe acute malnutrition. First, Amoxicillin reduced the risk of hospitalization when compared to placebo, but about 53% of children transferred to inpatient care were admitted to the hospital for malnutrition. Next, among hospitalized children, there was no significant differences in mean of stay between the placebo group and intervention group, but both groups recovered at the same times. Despite these findings, researchers were able to conclude that amoxicillin reduced the risk of transfers to inpatient care due to complicated gastroenteritis and showed benefits over short-term weight gain.

From this study, it seems that overall Amoxicillin did not show superiority to placebo treatment. These findings challenge the view that routine antibiotic therapy is always necessary or beneficial for the treatment of severe acute malnutrition. Eliminating the use of Amoxicillin could help simplify the treatment regimen, which would result in increased cost savings associated with drugs, staff, and systems for delivery. In addition, there are multiple factors that can be costly to treat, such infections that result from resistance to antibiotic regimens. I believe that it’s good that these researchers decided to check the treatment guidelines for using amoxicillin, because determining the true value of the regimen and be greatly beneficial for the future treatment of severe acute malnutrition. Do you believe it is important to routinely research established treatment guidelines? Why or why not? Are you aware of any treatment guidelines that have been updated in the past few years?

Isanaka S, Langendorf C, Berthe F et al. Routine Amoxicillin for Uncomplicated Severe Acute Malnutrition in Children. N Engl J Med. 2016; 374:444-453

Fish Intake in Pregnancy and Child Growth

Fish are commonly exposed to persistent organic pollutants, which may have endocrine-disrupting properties that contribute to obesity development. Fish intake of pregnant mothers has been shown to increase fetal growth, but this study set out to see if increased fish consumption affects child obesity as well.

Over 26,000 woman through the span on 15 years were studied through childbirth and followed up with every two years until the child was 6 years old. The results were that woman who consumed fish more than 3 times/ week gave birth to children with higher BMIs compared to those children whose mothers consumed fish less than 3 times/ week. The high fish intake mothers had children who had increased risk of rapid infant growth as well as increased risk for obesity at 4 years and 6 years old.

FDA advice on fish consumption in woman who are pregnant, breast feeding, or thinking about becoming pregnant changed in June of 2104 to match the data found in this trial. FDA now recommends for pregnant woman to consume more fish due to its cognitive benefits for their offspring, but to consume no more than 3 meals of fish/ week.

As pharmacists, we deal with a variety of factors that impact our patients health. Fish oil supplements as well as diet is something that we need to consider when counseling maternal populations.

Link to Article

Stratakis N, Roumeliotaki T, Oken E, Barros H, et al. Fish intake in pregnancy and child growth. JAMA Pediatr. 2015. doi:10.1001

Prescription Use Among Children with Autism Spectrum Disorders

The purpose of this article is to focus on the difference between prescription medications given to children with autism spectrum disorders versus children in the general population. Published in February 2016, this article focuses on a study that was conducted during the years 2007-2010. This study was a cross-sectional study of ambulatory prescription fills from Maine, Vermont and New Hampshire.

Autism Spectrum Disorders, or ASDs, affect more children than we may think. In fact, during this study, there were 13,100 children diagnosed with ASD, compared to the 936,721 children without ASD diagnosis. That means that about 1 in every 71 children is diagnosed with ASD. Also, along with the ASD diagnosis comes prescription medications. Furthermore, this study showed that children with ASDs consume more prescription drugs than the general pediatric population.

The overall prescription fill rate was about 4-fold higher in children with ASD compared to the children without ASD. First, psychotropic use among children with ASD was 9-fold higher than the general population rate. The children with ASD made up about 2% of the pediatric population, but received a little over 15% of the psychotropics being prescribed to those pediatric patients. Next, nonpsychotropic drug use was also higher in the population with ASD, particularly in those children age 3 or younger. Furthermore, antibiotic use was 2-fold higher and antacid use was nearly 5-fold higher than the general population.

This increase in drug use was not only observed in the community settings, but also seen in the hospital settings. Antacid and alpha-agonist uses in hospital settings were about 3-fold higher in the ASD population, and benzodiazepines reached nearly 4-fold higher for the ASD population in the hospital setting.

As you can see, autism spectrum disorders really affect the medication use in the pediatric population. There is an overall increase in psychotropic and nonpsychotropic prescription medications in the ASD population, followed by an increase in other prescription drugs as well. There is still more research to be done in this category; however, the correlation is shown relating ASD with prescription drug use as compared to the general population.

Prescription Use among Children with Autism Spectrum Disorders in Northern New England: Intensity and Small Area Variation. House, Samantha A. et al. The Journal of Pediatrics , Volume 169 , 277 – 283.e2

Methylphenidate for ADHD in children and adolescents

Methylphenidate is often prescribed to children and adolescents for the treatment of ADHD, or attention-deficit/hyperactivity disorder, however, there is no known comprehensive systematic review on the harms and benefits of administering the medication to the young patients.  Previous reviews have bias or contain flaws, thus, this research study agrees to use guidelines following the Cochrane Handbook and PRISMA guidelines.  Full texts of randomized clinical trials that compared methylphenidate with or without a placebo in the age range of about 3 to 18 years were selected.  Pharmaceutical companies were contacted for additional information.  Primary outcomes included serious adverse effects and symptoms of ADHD, while secondary outcomes included non-serious adverse effects.  No patients were involved in the study.  The data was extracted from the trials by reviewers and the authors were contacted for more information.  The dose of methylphenidate, design of trials, bias, sex of participants, type of ADHD, and other factors were analyzed in the clinical trials.  Concerning quality of evidence, the potential levels of bias associated with the trials evaluated.

Out of 14,431 records, 761 of the publications were included in this review.  In the results, a high possibility of bias was found in most trials due to the passion, failure of full coverage blinding, choosy in reporting data, etc.  Thus, although many of the outcomes suggest that methylphenidate shows benefits, this cannot be deemed as a true conclusion due to the high risk of bias associated with many trials.  Conclusions show that symptoms associated with methylphenidate may be improved and may not cause increase serious adverse effects.  However, methylphenidate may result in a high risk of non-serious adverse effects, such as decreased appetite and sleep problems.

I hope to see a future trial that has little risk of bias, which accounts for all the adverse effects that occur as a result.  This could help with children and adolescent patients who are currently diagnosed with ADHD and could potentially unveil that they are not receiving the benefits that they believe they are supposed to receive.

BMJ. 2015 ; 351(5203): .


Endocrine Effects of Inhaled Corticosteroids in Children

The effectiveness of inhaled corticosteroids (ICSs) in treating various chronic respiratory illnesses, such as allergic rhinitis, asthma, and cystic fibrosis, has increased over the years. Newer devices and formulations of the inhaled drug have reduced local adverse effects, but the improved delivery of the drug to the lungs increases systemic absorption and consequently can present a new set of adverse effects. This review article reviews the range and severity of these effects in children and sites various recommendations for prescribers and health care professionals when giving such inhalants.

The most serious potential adverse effect that can result from inhaled corticosteroids is adrenal insufficiency. Long term use of ICSs in children can lead to bone mineralization, DM1 and DM2, obesity, and this insufficiency, or suppression of the hypothalamic-pituitary-adrenal. The authors reviewed a case study on a 7-year-old female that presented with a new onset seizure due to adrenal insufficiency after using an inhalant regimen to treat her asthma. They concluded that clinical effectiveness of inhalants and systemic absorption have a strong positive correlation that can only be partially explained by the device and formulation modifications of the drug. Conclusions and research were also done on the drugs’ effects on bone mineral density, which were found to be mild, and suppression of linear growth, which were found to be slightly correlated. The article presents that generally, inhaled corticosteroids are safe and effective drugs, but life-threatening endocrine effects can occur even with normal doses. It is suggested that reducing systemic adverse effects could require increasing drug protein binding and rapid clearance time, as well as decreased lipophilicity.

This article brings to light something that most parents of children using inhaled corticosteroids are unaware about. I think that using education in this case is probably the best way to avoid this problem, seeing as inhaled corticosteroids are the most effective treatment in reducing respiratory distress. Pharmacists caring for children that routinely use ICSs could really play a major part in watching for adverse endocrine effects by providing correct dosing schedules and learning about how often patients use their inhalers.

JAMA Pediatr. 2016;170(2):163-170. Link to Article


Drug Dosing and Pharmacokinetics in Children With Obesity

A sixth of children in the United States are affected by obesity. When a person is obese, their body composition and physiology is altered, which results in a change in effects associated with drug dosing and pharmacokinetics. Thus, the effect of  drug disposition on obesity can possibly lead to therapeutic failure or toxic side effects. Although this fact is well known, there is little information known about the effect of childhood obesity of drug pharmacokinetics. Currently, there is no comprehensive, evidence based understanding of the effect of childhood obesity of drug pharmacokinetics. Thus, researchers conducted a systematic review to find studies in the last 40 years that provided evidence of the effect of obesity on drug disposition in children. They searched literature databases to find if any studies contained data on drug clearance, volume of distribution, or drug concentration in obese children.

Researchers were able to discover 20 studies in the last 40 years that met the inclusion criteria and contained pharmacokinetic data for 21 drugs. Out of these studies, 11 out of 17 drugs had clinically significant pharmacokinetic alterations observed in children with obesity. In addition, for 5 out of 13 drugs studies showed that pharmacokinetic alterations resulted in substantial differences in exposure between children with and without obesity. Overall, studies indicated important obesity-related changes in drug pharmacokinetics. However, there were many limitations associated with these studies. For example, the majority of studies included small numbers of children. Furthermore, many drugs that were studies are not commonly prescribed drugs. There was no data for several important drug classes where obesity-related toxic overdosing or subtherapeutic underdosing may have been previously observed in adults, such as in acute care, cardiovascular, and anesthesia.

After reviewing these articles, researchers concluded that the relative information available about the drug pharmacokinetics of children who are obese is concerning, because it is so limited. To account for physiological and pharmacologic factors, some physicians adjust weight-based dosing using various metrics of body size, such as ideal body weight. However, this dosing strategy is largely based on theory or extrapolated data from studies in adults. Some analyses have identified that these dosing strategies may give false predictions of clearance and other pharmacokinetic values. To address this issue, researchers are currently collaborating with the National Institute of Child Health and Human Development in a systematic review of acute care and commonly used drugs to develop a pharmacokinetic database for obese children. As a result, data generated from this review will be utilized to make appropriate dosing recommendations for obese children. For future studies about pharmacokinetics in obese children, researchers hope to focus on including drugs if different therapeutic drug classes, based on drug use, medical need, and expected pharmacokinetic alterations in obesity (based on adult studies).

After reviewing this article, I was surprised to find that there were very few studies published about the pharmacokinetic factors of drugs in obese children. Since there are many children who are obese in the United States, I believe it is important to discover the pharmacokinetic parameters of drugs in obese children. With more information available, pharmacists and physicians will be able to better treat these children. Did you find this article surprising? Why or why not? Do you have any thoughts on why there have not been many studies published about childhood obesity and drug pharmacokinetics?


Harskamp-van Ginkel MW, Hill KD, Becker KC, et al. Drug Dosing and Pharmacokinetics in Children With Obesity: A Systematic Review. JAMA Pediatr. 2015;169(7):678-685.


Antidepressants may double the risk of aggression and suicide in children

It is has been researched that suicidal behavior may be increased with children aged <18 who take popular antidepressants such as SSRIs and SNRIs, however, few systemic research has been done to correlate the effects of aggressive behavior with popular antidepressants.  This systematic review and meta-analysis was conducted to analyze the mortality, suicidality, aggression, and akathisia associated with five popular antidepressants—duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine—using clinical study reports.  Akathisia is an extreme state of restlessness, agitation, and distress that can increase the risk of suicide and violence. No patients were involved in the study.  The methods included obtaining clinical study reports from the European Medicines Agency and Modern Humanities Research Association.  Out of the 198 clinical study reports, only 68 were used.  Using the reports that contained double bind placebo controlled trials and patient narratives, primary outcomes (mortality and suicide) and secondary outcomes (aggressive behavior and akathisia) were assessed by searching for specific terms, such as those used by the FDA.

Quality of the clinical study reports were varied, such as the number of trials conducted and the length of the study designs.  The results of the study showed that 16 deaths occurred in adults, and 155 suicidality events occurred with an odds ratio in children and adolescents doubled to that in adults.  The odds ratio for children and adolescents was also double that to adults for aggressive behavior.  The odds of akathisia were roughly the same for both adults and children and adolescents.  Thus, the data from this study shows that there is indeed an increased risk of suicide in children and adolescent taking antidepressants.  However, the study also found that there was a significant increase in aggressive behavior in children and adolescents.  This was a comprehensive review of randomized controlled trial data and is the first to note this finding of increased aggressive behavior.

My questions posed to colleagues are: Do you feel that this is a significant, valuable finding, despite the limitations in the research study?  Do you feel that this information could benefit pharmacists, and if so, how?

BMJ. 2016; 352(65): .