Safety Concerns Surrounding Quinolone Use in Children.

In a study published in The Journal of Clinical Pharmacology, the clinical use of fluoroquinolones to treat infections in children beyond a few select and extreme indications, most notably anthrax inhalation, is examined. The paper attempts to elucidate the existing challenges for clinicians in assessing both the risks and benefits when prescribing fluoroquinolones to children based on the currently available safety data and drug label restrictions.

Fluoroquinolones are extremely common in adult treatment because they have proven to be highly effective in the treatment of infections due to their broad spectrum of activity, excellent tissue and intracellular penetration, high oral bioavailability, and overall good tolerability profile. However, studies from the beginnings of fluoroquinolone development show that juvenile animal subjects showed the development of damage to immature cartilage of weight-bearing joints. Because of concerns raised about similar effects in infants, pediatric fluoroquinolone studies were halted.

The study found that the only frequent musculoskeletal adverse events observed in neonates, infants, and children are transient arthralgias that resolve themselves soon after discontinuation of fluoroquinolone therapy. Of course, risk of emerging bacterial resistance is also a concern with administration of fluoroquinolones in the pediatric population, though it presents no more threat than the same risk in adult populations due to over use of the drugs. Optimization of fluoroquinolone use should always be considered when implementing antimicrobial therapy as to limit unnecessary administration.

Citation:

Patel K, Goldman JL. Safety Concerns Surrounding Quinolone Use in Children. Journal of Clinical Pharmacology. 2016 Feb 10. doi: 10.1002/jcph.715. [Epub ahead of print]

In utero Exposure to β-2-Adrenergic Receptor Agonist Drugs and Risk for Autism Spectrum Disorders

Autism Spectrum Disorders (ASD) have received much media attention regarding supposed links between them and childhood vaccines. While this association is false, there may be evidence to support an association between maternal use of B-2-adrenergic receptor (B2AR) agonists and child development of ASD. Previous studies support a correlation between the two, but they do not show whether the drug or the mother’s condition is causal. Evidence on the mechanism of B2AR agonists also supports the association between their use and ASD.

Researchers from Drexel University sought to further research a possible link between B2AR agonist drugs and ASD by performing a case-control study on children born in Denmark between 1997 and 2006. Cases were considered to be any children diagnosed with childhood autism, atypical autism, Asperger syndrome, and pervasive developmental disorder- unspecified, while controls were considered anyone without these diagnoses. Ten controls were matched with each case based on birth month and year, so in total there were 5,200 cases and 52,000 controls. Children were considered exposed to B2AR agonists if there was maternal use any time between 90 days before the estimated conception date and the delivery date.

The study found that 3.7% of cases were exposed to B2AR agonists and 2.9% of controls were exposed to B2AR agonists during pregnancy. Thus, the researchers concluded that exposure to B2AR agonists during pregnancy was associated with an increased risk for ASD and that the risk was similar for exposure in the first, second, and third trimesters. However, less than 1% of cases of ASD could be attributed to the exposure to B2AR agonists, if their use is in fact a cause of ASD.

This study interested me because it looked into a potential correlation between autism and medications that I have not heard of previously. I am curious to see whether articles like this one will have as large of an impact on media portrayals of autism and its causes as the false article on the causal relationship between autism and vaccines has had. I am also interested in seeing if this research has any effect on the use of B2AR agonists in pregnant women or if the benefits of the medication always outweigh the risks to the child.

 Pediatrics. 2016; 137 (2): 1-8.

Standardizing ICU management of pediatric traumatic brain injury is associated with improved outcomes at discharge

While considerable medical research has been done involving the treatment of traumatic brain injury (TBI) in adult patients, much less is known regarding treatment of TBI in pediatric patients, due to differences in CNS response. Guidelines for treatment in pediatric patients are summarized in the Brain Trauma Foundation guidelines, which were most recently updated in 2012. However, O’Lynnger et al. describe the need for further treatment standardization.

In their retrospective study of 128 pediatric patients with severe TBI from April 1, 2008 to May 31, 2014, the authors compared short-term outcomes before and after treatment was standardized on April 1, 2013. Goals of treatment for TBI include limiting secondary brain injury by increasing cerebral blood flow. Discharge disposition (either home, to rehabilitation, or death) and Glasgow Outcome Scale scores were used as measures of patient outcomes.

Following standardization, O’Lynnger et al. report favorable outcomes (i.e., discharge home) for 69 percent of patients, compared to 36 percent pre-protocol. In addition, this protocol reduced the number of patient deaths by 10 percent. Only one patient was discharged to rehabilitation during the study. Patients’ length of stay was similar before and after protocol implementation.

From these results, we can conclude that implementing standardized treatment for severe TBI in pediatric patients can improve short-term outcomes. This article is important because it highlights the need for additional medical research involving the treatment of TBI in pediatric patients. Also, by demonstrating the benefits of standardizing treatment for TBI, the authors urge further standardization in pediatric critical care units.

J Neurosurg Pediatr. 2016;17(1):19-26.

Use of Erythropoietin and Darbepoetin in Improving Brain Development in Premature Infants

Infants born with an extremely low birth rate have the potential to develop neurodevelopmental disabilities, such as cerebral palsy (CP), mental disabilities, and learning and attention deficits during school age. As of today, successful neuroprotective interventions have yet to be developed, but a group of scientists have found that two drugs, erythropoietin and darbepoetin, have a strong potential to have neuroprotective effects in infants.

Erythropoietin and darbepoetin are in a class of drugs called erythropoiesis stimulating agents (ESAs), which have been used clinically over 20 years to help stimulate red cell production. Erythropoietin stimulates red blood cell production in adults who have anemia attributable to end-stage renal disease or cancer. Darbepoetin is a biologically modified long-acting ESA that allows dosing every 1 to  4 weeks due to the increased half-life of the drug. Darbepoetin is also used for adults with anemia attributable to end-stage renal disease or cancer. In addition, darbepoetin was shown to have a similar half-life in infants. Premature infants also lack the ability to make new red blood cells so they often need frequent blood transfusions to replace blood taken for lab tests. However, use of erythropoiesis stimulating agents are shown to decrease the number of blood transfusions in premature infants.

In this research study, scientists performed a randomized, masked, and multicenter study comparing erythropoietin, darbepoetin, and placebo given through 35 weeks post conceptual age, with transfusions administered according to protocol. The surviving infants were evaluated at 3.5 and 4 years of age, and the primary outcome was the infant’s composite cognitive score. Assessments of full-scale IQ, general language, and overall measure of executive function, on the basis of tests evaluating inhibitory control and spatial working memory, were conducted.

Rather gathering data, scientists would that the infants randomized to receive the ESAs had better cognitive outcomes compared with placebo recipients at 3.5 and 4 years of age. Specifically, they scored about 12 points higher on average on IQ tests than the untreated infants, but about 10 points lower than the normal weight infants. Furthermore, on tests measuring memory and impulsive behavior, the treated infants had similar results as the infants born at normal weight.

This study mostly examined white and hispanic infants, so larger studies that include more diverse patient populations are needed to determine whether ESAs can help a broader range of infants. Thus, it is still too soon to recommend the medicines for treating developmental delays. However, treatment for medical problems and developmental delays due to prematurity has not kept pace, so this particular finding was significant.

I am glad to see that there are steps being taken to study the developmental delays in premature infants. Possibly in the future, parents can be relieved that their premature infants will be able to avoid potential developmental issues. However, in the future, I hope that there will be more research focusing on other developmental issues associated with premature birth. Do you believe that this finding will have a large impact in the future? What other areas of study related to premature birth do you think researchers should focus on in the future?

Source:

Ohls, R. K., Cannon, D. C., Phillips, J., et al. Preschool Assessment of Preterm Infants Treated With Darbepoetin and Erythropoietin. Pediatrics. 2016

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

http://www.jpeds.com/article/S0022-3476(15)01199-3/fulltext

Controversy of Childhood Vaccinations

Childhood vaccinations have become a point of controversy among parents and physicians. Due to a more recent outbreak of measles and other childhood diseases in America, the American Academy of Pediatrics has urged parents to vaccinate their children more than in the past. Speculation about vaccinations was generated after a falsified report by Andrew Wakefield was published claiming there was a connection between the measles vaccine and autism. The paper was been withdrawn and Wakefield has been eliminated from the General Registrar, however the fabricated data still has a massive presence in the decision making process for parents. Because parents have sole decision-making power, physicians can only make recommendations through counseling in order to obtain informed consent.

In order to reverse the negative connotations surrounding childhood vaccinations, physicians and medical professionals must take on the role to educate the parents prior to their decision-making. They must emphasis the purpose of vaccinations, which is to prevent the child from diseases that may cause mortality or major morbidity. It is up to the physician to strongly recommend and urge the parents to approve vaccinations for their children. The American Academy of Pediatrics recommends that in addition to educating the parents, the physicians must call on their ethical responsibility to their children, which means emphasizing the clinical benefit to not only their children but also to the other children that will come in contact with their own child. In conclusion, it is up to medical professionals to remove the negative stigma of vaccines and reinforce the positive benefits to each parent and patient.

J Pediatr. 2016;169(305-309)

Improving Pediatric Outcomes in Oncology through Genomics

Within the past decade, target therapies have been prescribed using genomic data to more precisely diagnose cancer and predict future outcomes. The pediatric field is lacking by not targeting mutated oncogenic drivers and rare ALK translocated malignancies. Pediatric cancer does not have as many mutations, and many studies on focused on the disease state. New evidence shows that post therapy relapse samples accumulate more mutations and may lead to chemotherapy resistance.

A study with 102 children and young adults (up to age 22) involved exam sequencing of paired blood mononuclear cell and tumor DNAs along with tumor RNA sequencing. 69% had solid tumors. The study was designed to identify germ-line mutations that could cause an effect, tumor-specific alterations that would alter the histopathologic diagnosis, change risk status or both, and medically targetable somatic mutations.

Potentially actionable findings were found in 46% of cases and action was taken in 23 of those 42 patients (54%). A change of therapy was initiated for 14 patients (15%), a gremlin mutation was found to be clinically relevant in 9 patients, and 9 of the 14 patients had clinical benefit from the intervention.

This data is very relevant and suggests a promising field of research. With genomic sequencing, therapies were personalized in order to better target the cancer. As pharmacists, we should consider this and acknowledge that patients may require different treatment even with the same disease state. The research and sequencing in adults can and should be applied to children to better care for their cancer.

JAMA. 2015;314(9):881-883. 

A prospective three-step intervention study to prevent medication errors in drug handling in paediatric care

Each year, the United States emergency department treats up to 158,520 children for adverse drug effects. According to previous studies, up to 21$ of these are caused by medication errors. In this study, researchers performed a prospective intervention study in the University of Heidelsberg’s children hospital. 18 beds were systematically studied through a three-step intervention to prevent medication errors in the drug-handling processes.

Each step of the intervention was directed at different causes of errors. After three interventions, there was a significant decrease in the frequency of errors performed by the nurses, from 91% to 26%. There was also a decrease from 88% to 49% in the number of patients who were exposed to at least one medication error. It is evident that the three step intervention decreased the amount of medication errors in the hospital setting.

This study is important and interesting because while performing pediatric care, it is necessary to be certain of what medications the patient needs administered. Implementation of this three-step intervention in other hospitals around the world will decrease the amount of emergency visits children take. It is worth it in the end to take the extra precautions to reassure that the medication being administered to the patient is correct.

Niemann D, Bertsche A, et al. A prospective three-step intervention study to prevent medication errors in drug handling in paediatric care. Journal of Clinical Nursing. 2015;24:101-14.

http://onlinelibrary.wiley.com/doi/10.1111/jocn.12592/full

Emergency Procedural Sedation With Propofol in Older Teenagers: Any Cause for Concern?

Often in emergency departments there is a need for fast, short-term sedation so that necessary procedures can be performed.  A common sedative used for this purpose is propofol, which is delivered intravenously and can be adjusted to varying doses to provide the appropriate level of sedation.  Use of propofol in youth has been uncommon; emergency departments typically utilize ketamine in these cases.  This study sought to find out whether propofol would be appropriate for use in 16-19 year olds because ketamine becomes less favorable as patients grow older.

The study looked at 4,063 emergency department procedural sedations, including 230 teenagers, 2,835 adults, and 980 senior citizens.  The study concluded that the teenage group was in fact less likely to experience hypotension as a side effect when compared to the other age groups, and all groups had a similar satisfaction with treatment.  The study also confirmed, “there were no recorded episodes of arrhythmias or of apnea lasting longer than 30 seconds.”

These results demonstrate that propofol is safe and effective in patients ages 16-19; however, the journal article notes that “drugs and therapeutics committees frequently restrict access to propofol to the operating room in pediatric facilities.”  The results from this study could have a large impact in patient care and emergency department regulations and procedures.  It opens the possibility of a very favorable sedation mechanism for use in a new age range of patients.  It will be interesting to see how the restrictions of pediatric emergency departments change in response to this new data.

 

Campbell SG, MacPhee S, Butler, M, et al.  Emergency Procedural Sedation With Propofol in Older Teenagers: Any Cause for Concern?  Pediatr Emerg Care.  2015;31:762-765.

http://ovidsp.tx.ovid.com/sp-3.18.0b/ovidweb.cgi?&S=OCGOFPNKJBDDEEIINCJKLGFBMPILAA00&Link+Set=S.sh.21833_1455116825_21.21833_1455116825_33.21833_1455116825_41.21833_1455116825_43.21833_1455116825_47.21833_1455116825_51%7c6%7csl_10

The Obesity Epidemic- Understanding the Disease and the Treatment

Childhood obesity has been a hot topic in recent years. From Michelle Obama’s program to reconstruct school lunches to the many childhood fitness centers opening up, the health of our future has been on everyone’s mind. The prevalence of childhood obesity has risen from 4% to 6% from 1999-2004 to during 2011-2012 as stated in the article. Our children’s chances for more serious diseased states in their later years is increasing with every incidence of severe childhood obesity.

In this editorial, there is good evidence showing that obesity can be considered a disease that is initiated by interactions of genetics and the environment. Around 90% of children with severe obesity will become obese adults. The disease may start off as a lifestyle problem, but it can rapidly lead to energy-balance imbalances. In a way, the body sets a new body-weight set point and continues to try to maintain that.

It’s most important to note that none of the medications that have recently been approved and studied in adults to lower body weight have been studied in children. These drugs such as phentermine, lorcaserin, liraglutide have no evidence backing their use in the younger obese population. This puts a damper on the treatment of childhood obesity and the prevention of what disease states await these children. Bariatric surgery has been used on some adolescents as a means of sustained weight loss. But, the risks and benefits have yet to be closely analyzed in this population. There are social benefits to the patient but longitudinal studies of these patients still has to be done to establish if there are any long term risks. The main point of the article is that obesity is difficult to manage and prevention is one of the best and only ways that we can safely target our adolescent and child population against this disease. Lifestyle interventions should be closely instituted in children and followed through during their learning ages to best equip them to make the healthiest and safest decisions in their lives.

Knowing that lifestyle is one of the biggest preceptors to childhood obesity, should the parents of obese children be instructed to take parental guidance classes to help themselves and their children make healthier lifestyle changes?

 

 

Citation:

N Engl J Med. 2016; 374:177-179

http://www.nejm.org/doi/full/10.1056/NEJMe1514957