A Cohort Comparison of Buprenorphine versus Methadone Treatment for Neonatal Abstinence Syndrome

Neonatal abstinence syndrome (NAS) occurs when newborns are exposed to opioids while still growing in their mother’s womb. Most of the common addictive opioids are able to cross the placenta and the baby begins to go through withdrawal when they are born and no longer receiving the drug. Symptoms of the syndrome depend on the drug the infant was exposed to. One treatment of NAS includes giving the child a similar opioid and continually decreasing the dose in order to wean the child off and help with withdrawal symptoms.

Hall and colleagues preformed a retrospective cohort study in which they looked at the treatment of newborns suffering from NAS. They looked at 6 hospitals in the southwest Ohio area from Jan. 2012 to Aug. 2014. 201 patients were treated for NAS in the study, 38 treated with buprenorphine and 163 treated with methadone. The researches found that the treatment of sublingual buprenorphine for NAS was associated with a shorter average treatment days and hospital stay. Buprenorphine treatment duration was 9.4 vs 14.0 days for treatment with methadone. Average hospital duration for buprenorphine treated infants was 16.3 days, and methadone was associated with an average stay of 20.7 days. A definite conclusion was not made that buprenorphine was the best treatment for NAS, but the study did prove that buprenorphine was superior to methadone in the treatment of NAS in newborns.

Working as an intern at a community pharmacy I see patients on buprenorphine, and other opioids every day. This article really hits home because I have seen so many mothers, with multiple children, picking up prescriptions for buprenorphine. Most have been on the prescription for a long time and don’t seem to be weaning off of it. I wonder what we as future pharmacists could do in order to try and prevent or lower the numbers of newborns experiencing NAS because of their mothers opioid addictions.

J Pediatr. 2016;170:39-44. http://www.jpeds.com/article/S0022-3476(15)01451-1/pdf.

Asenapine for the Acute Treatment of Pediatric Manic or Mixed Episode of Bipolar I Disorder

Asenapine, brand name Saphris, is a sublingual tablet that is FDA labeled for the treatment of bipolar disorder and schizophrenia. Like most antipsychotics, the exact mechanism of action is unknown, just that it acts on dopamine receptors in the brain. Findling and colleagues preformed a double-blind placebo controlled study in which they studied the use of asenapine for the treatment of manic or mixed episode bipolar disorders in children aged 10 to 17 years old. The doses included placebo 2.5 mg, 5 mg, and 10 mg twice daily and they were distributed to the patients in a 1:1:1:1 ratio. 403 patients were included in the study, so about 101 patients received each dose. The results were measured based on the Young-mania rating scale (YMRS). The YMRS is a rating scale based on the patient’s subjective view of his or her manic symptoms in the last 48 hours. The YMRS was assessed after 21 days of the assigned medication strength.

The average YMRS rating is 12 and the results showed that after the 21 days the average difference in YMRS for those with the placebo controlled versus the asenapine doses were -3.2 for the 2.5 mg, -5.3 for the 5.0 mg, and -6.2 for the 10 mg. In contrast to the average improvement in the YMRS, there was significantly more adverse effects experienced by those taking the asenapine doses. These adverse effects include somnolence, sedation, increased appetite, weight gain, and increased fasting blood glucose levels. The researchers also looked at the presence of ADHD and if the symptoms were changed, which they were not.

The researchers concluded that asenapine is superior to the placebo with the improvement of YMRS scores and was very well tolerated, even with the increase in side effects.

This is really interesting, and relevant to our learning in top drugs currently. This is not one of the antipsychotics we are learning about specifically, but its really interesting to see actual data for the use of an antipsychotic, especially on kids. I wonder if there have been studies done that look to see if antipsychotics affect the brain development of these children as they grow.

J AM ACAD CHILD ADOLESC PSYCHIATRY. 2015;45(12):1032-1041.


Adverse Events After Routine Immunization of Extremely Low-Birth-Weight Infants

Vaccines in child has been a controversial topic in the media, and in the public. As health care professionals we usually role our eyes at the topic of parents not vaccinating their children.

DeMeo and colleagues researched adverse effects in low-birth weight infants 3 days before they receive immunizations and after they receive them. Immunizations in low-birth weight patients have shown a positive impact on the child’s immune system through the rest of their childhood, but dangerous adverse effects do occur. This creates a dilemma for physicians: immunizations are very beneficial, but are they beneficial enough to give early on in the life of a low-birth-weight infant to risk death in some low-birth weight infants?

DeMeo and colleagues preformed a multicenter retrospective cohort study that included 13,926 infants that were born at 28 weeks gestation or earlier. The infants were discharged from 348 different neonatal intensive care units from Jan. 1st, 2007 to Dec. 31,2012. Each of these 13,926 patients received one or more immunization between 53 days to 110 days after birth. Their measurements included the appearance of sepsis, increased need for respiratory support, intubation, seizures, and death in the infants. 91.1% of the infants received three or more immunizations and the results from pre-immunizations to post include:

Increase from 5.4 per 1000 days of patient days experiencing sepsis to 19.3 per 1000 days.

Increased respiratory need: 6.6 to 14.0 days per 1000 days

Increased intubation need: 2.0 to 3.6 days per 1000 days

Adverse effects were similar for all immunization types and were even more prevalent in infants born at 23 or 24 weeks. The researches did find that immunizations are causing increased adverse effects in low-birth-weight infants. They did not come to a definite conclusion that patients should not be receiving immunizations or say that the reward is greater than the risk. They suggested further investigation into whether spacing and timing of the immunization administration of the immunizations played a role in the increase of adverse effects.

This article was really interesting because it brought a topic that is controversial and showed some evidence that in some instances immunizations can be harmful. Seeing here that they can cause adverse effects as serious as death is frightening.

JAMA Pediatr. 2015;169(8):740-745.


Detection of Circulating miRNA Levels in Schizophrenia

Schizophrenia is a mental disorder that can effect a person’s entire life: how they think, feel, and behave. Like other mental disorders its symptoms can be disabling. The disorder most commonly begins to show symptoms between the ages of 16 and 30 and the symptoms are divided into three categories: positive (psychotic behaviors), negative (disruption to normal emotions), and cognitive (changes in memory and thinking). It has been long known that genetics is a risk factor for development of the disorder, with multiple genes increasing the risk. A singular gene has not been found to cause the disorder itself, and diagnosis is currently only based upon symptoms. This past November, Wei and colleagues investigated whether the presence and concentration of circulating miRNA can become a diagnostic biomarker for Schizophrenia. miRNA are noncoding short RNA sequences that regulate gene expression and a variety of other cellular functions.

Two cohort studies were used in determining results. The first included 164 patients with schizophrenia and 187 control subjects. The plasma miRNA for each patient was profiled using three different genetic based technologies (Solexa sequencing, TaqMan Low-Density Array, and qRT-RCR). It was studied based on the expression signals.

The qRT-PCRs in the first were then compared with qRT-PCRs in the second which included 400 patients diagnosed with Schizophrenia, 213 control patients, and 162 patients with a nonschizophrenia psychiatric disorder.

Both studies revealed 8 miRNAs that were up-regulated in the patients with Schizophrenia. There were even two miRNAs that were upregulated in Schizophrenia but not in nonschizophrenia disorders. The two miRNAs were miR-130b and miR-193a-3p. Finding that these are upregulated, there is a potential for the development of a diagnostic biomarker, and even a drug therapy target.

Mental disorders are very hard to diagnosis and the possibility of a potential biomarker for a disorder that has previously only been able to be diagnosed by symptoms is very promising for those that may be affected by it. The knowledge of this is also a potential for drug target treatment and maybe even prophylaxis. Personally knowing someone who suffers from Schizophrenia, this really hit home and gave my a little hope for the future of those who are already affect and those who may be in the future.

Am J Psychiatry. 2015;172(11):1141-1147.

Depression in Childhood and the association of Cortical Grey Matter Development

In early childhood the volume of cortical grey matter in the brain increases significantly, and then begins to decrease again after puberty. The decrease in thickness is a very selective elimination and demyelination. This period “U-shaped trajectory” is very important and has been found to be associated with cognition and emotional function. Luby and colleagues decided to study the effects that early childhood depression has on the cortical grey matter development in adolescence.

The trail design included 193 children from St Louis, Missouri, aged 3 to 6. They were studied in a longitudinal study for 11 years (Sep. 2003 to Dec. 2014). The data collected was behavioral and neuroimaging and trajectory was measured based on volume, thickness, and surface area. These were analyzed to study the association between depression symptoms and previously diagnosed major depressive disorder with the trajectory of cortical grey matter. The study found that there was an association between an episode of major depressive disorder in childhood with grey matter volume loss (slope of -0.93cm^3) and thinning (slope of -0.0044mm). Both were found to be significant findings. On the other hand there was no association found with family history of major depressive disorder or a traumatic life experience.

This study was shown to really highlight the significance of childhood depression and neural development. I think its really interesting that children so young are experiencing major depressive disorder. A study should be done, if not already, in order to determine if depression rates have increased in children over the past few decades. I do not think that medications are always the answer for children, but I do believe that we need to find the root of the problem and begin there. If this depression is making such an impact on the development, then it could be associated with many problems down the road for individuals. This study shows that if major depressive disorder can be prevented in children, problems down the road with cognitive and emotional abilities.

Jama Psychiatry. 2016;73(1):31-38.

Association between physical activity and the duration of concussion symptoms

Concussions have been a big debate in the world of sports medicine. This month Howell and colleagues published a cohort study, which is a longitudinal observational study, that looked at the association between physical activity and symptom durations of a concussion. The study began with 364 patients that were seen by a doctor within three weeks of being diagnosed with a concussion. Each patient completed a questionnaire that ask questions regarding a post concussion symptom scale, prior concussions, loss of consciousness or amnesia, and prior treatment received for headaches. At later follow-up appointments each patient self-reported their own levels of physical activity. The data was complied and a model was created to determine the association between initial responses, reported physical activity, and symptom duration. They found that the participants aged 13 to 18 had shorter symptom duration with an increase in physical activity. These findings indicate that physical activity may not be detrimental to the recovery of concussion symptoms as previously thought in the medical world.

This is really interesting to me, because having been an athlete, it was always immediate protocol to halt physical activity after any signs or symptoms of a concussion. Seeing that stopping physical activity may not be completely necessary in younger individuals is against all that has been associated with concussion treatment and it is really surprising. There has been a lot of research on concussion prevention and treatment lately because of the seriousness of the injury. Seeing that some progression is being made is promising and even opens up the door to see if pharmacists can one day make an impact on concussion treatment.

Am J Sports Med. http://ajs.sagepub.com/content/early/2016/02/02/0363546515625045.abstract (published online 2 February 2016)

iCat in Pediatric Extracranial Solid Tumors

We hear about cancer related news almost every day, but pediatric cancer is unique because its targeted therapies are less available. Harris and colleagues just this past month studied the effects of individualized cancer therapy (iCat) recommendations and the feasibility of determining alterations in genomic sequences that can be targeted for treatment of pediatric extracranial (out side of the skull) solid tumors. The study was done from September 5, 2012 to November 19th, 2013 in 4 academic medical centers. There was also a one-year follow-up from the time of the visit. In order to be included in the study the patient criteria was 30 years of age or younger and with high risk, recurrent, or refractory extracranial solid tumors. Once selected, the tumors were profiled for their genetic sequencing. If an actionable alteration in the sequence was in fact present and iCat recommendation was made as long as an appropriate drug was available. Of the 100 participants it was found that 43 had results of potential clinical significance. They came to the conclusion that a clinical genomics study in pediatric oncology is feasible. It was also concluded that a large portion of pediatric solid tumors have actionable alterations in their genome.

Each case of cancer is different, especially in children. With new knowledge of certain places that we can begin treatment, such as an iCat, we are coming closer to an increase in survival rates. In my opinion there is still an immense amount of research that needs to be done, especially with pediatric cancer and stopping it from relapsing later in the child’s life. The use of genomics in this study really interested me because it is exactly what we talked about in class, targeted drug therapy. With the use of this I think we as the science community need to continue on looking at cancer and discovering drugs and therapies to overcome it. I believe that any tool that can help a health care professional make an informed decision on treatments is well worth it.


JAMA Oncol. http://oncology.jamanetwork.com/article.aspx?articleid=2484355 (published online January 28, 2016)

Pediatrics: Synbiotics for Prevention and Treatment of Atopic Dermatitis

Chang and colleagues conducted a meta-analysis of all published randomized clinical control trials that have been reviewed to study the use of synbiotics in the prevention/treatment of atopic dermatitis (AD) in pediatric patients. AD is a common condition in children and is more commonly referred to as eczema. It is characterized by dry and scaly red patches, usually occurring on the face of children. Chang and colleagues also describe AD as creating an environment that increases a child’s susceptibility to allergic diseases. Synbiotics are OTC medications that are a mixture of both prebiotics and probiotics. The clinical control trials must have met certain criteria in order to be included in the analysis. 8 of the 257 studies met the criteria of an oral administration intervention of synbiotics, and included the severity of the AD in the children within the trial. Of the studies used, 6 were for treatment of AD and 2 were the prevention. After a complete analysis of the 8 studies, evidence was found that synbiotics can be used to treat AD for children 1 year and older, but no significant evidence was found to support the use of synbiotics for AD primary prevention.

JAMA Pediatr. doi:10.1001/jamapediatrics.2015.3943 (published online 25 January 2016).

Parents have the most concern about newborns and what medications that they are receiving. They are also concerned about any disease that may affect their young children, and are willing to do anything in order to treat their children. This analysis shows that there is an effective oral treatment for AD in children, but do you think that this analysis alone is enough for a parent to agree to use as a treatment for their child’s AD? Pediatric medication use also has very strict guidelines in order to ensure the safety of children. In my opinion, I would be more inclined to give a child a topical medication that only interacts with the affected area before I would suggest an over the counter oral medication.