Late Surfactant Administration in Very Preterm Neonates With Prolonged Respiratory Distress and Pulmonary Outcome at 1 Year of Age

Because the lungs are one of the last organs to develop, their function is a major concern in infants born prematurely. Premature neonates may require mechanical ventilation if their lungs have not fully developed and they are not able to breathe sufficiently on their own. Mechanical ventilation (along with other factors) in infants can lead to an increased risk of developing bronchopulmonary dysplasia, which leads to chronic lung disease and abnormal neurodevelopment. Surfactant is a substance produced in the lungs that decreases surface tension in the lungs and stabilizes alveoli, ultimately preventing the lung from collapsing when exhaling. Surfactant can also be produced exogenously and can be used to treat premature infants.

This randomized, controlled, double-blind study examined the effects of late surfactant administration in 118 infants who were born before 33 weeks’ gestation and still required mechanical or high-frequency oscillatory ventilation at 14 days old. The primary end point was the time to first successful extubation; secondary outcomes were respiratory outcomes at 36 weeks postmenstrual age and at one year. Infants either received the treatment of surfactant or air. The results showed that the two groups were not significantly different in time to first successful extubation or respiratory outcomes at 36 weeks’ postmenstrual age. Bronchopulmonary dysplasia severity was also similar in both groups. There was a significant difference between the treatment and control in the number of hospitalizations required for respiratory issues at one year of age. The study concluded that surfactant was a safe therapy and that it did allow for better pulmonary outcomes at one year of age.

This study is just one example of the usefulness of synthesis of exogenous versions of endogenous substances to treat certain diseases. Although the study did not show overly successful outcomes, it was very logical to try to replace the substance that was missing in these infants, and this strategy could likely be used to find treatments for other diseases. Also, I really like seeing studies done in infants because they are an extremely vulnerable population and must be treated in different ways than adults or even children. I think it is very important to continue to do research on therapies specifically for infants.

 

JAMA Pediatr. doi: 10.1001/jamapediatrics.2015.4617 (published February 29, 2016).

Primidone Therapy for Essential Vocal Tremor

Essential vocal tremor is a neurologic disorder in which a tremor occurs when people try to speak. Because there are no pharmacologic treatments available for essential vocal tremor, it is very difficult to treat. Botulinum neurotoxin injections have been used to treat essential vocal tremor, but this therapy requires injections every 3 months and is painful and expensive. Primidone is a medication that has been shown to be an effective treatment for other types of essential tremor, so researchers in this retrospective study chose to investigate the efficacy of primidone for the treatment of essential vocal tremor.

This study included 30 female patients who were diagnosed with either essential vocal tremor or spasmodic dysphonia and were given primidone as a first line therapy. The end points of the study were whether the patients discontinued primidone therapy, whether they reported improvement of symptoms, and whether they moved onto botulinum neurotoxin therapy. There were 14 patients who reported an improvement in symptoms, 16 who did not discontinue primidone therapy, and 16 who went on to try botulinum neurotoxin therapy. In addition, 22 patients reported experiencing adverse effects from primidone. The adverse effects, small sample size, and limited improvements led the investigators to determine that primidone may be an effective treatment for essential vocal tremor, but more research on the long-term effects and efficacy needs to be conducted.

I found this article interesting because it investigated an off-label use of a medication that has been effective in treating similar conditions. While this article did not definitively prove the efficacy of primidone for the treatment of essential vocal tremor, it did provide some evidence for the use of the medication. Research on off-label uses of medications really intrigues me, and it seems like an important area to include a pharmacist in because pharmacists have an extensive knowledge of drug mechanisms and effects. In what ways do you think a pharmacist could have been included in this study or could be included in future studies of off-label drug uses?

 

JAMA Otolaryngol Head Neck Surg. 2016; 142 (2): 117-21.

Preoperative Narcotic Use in Patients with Crohn’s Disease

Crohn’s disease is an immune disorder that often causes people to experience chronic abdominal pain. To treat this chronic pain, many patients are given narcotics, which can cause immunosuppression, depression, anxiety, decreased quality of life, and increased disease activity in patients with Crohn’s disease. Another common feature of Crohn’s disease is that it comes with a high probability of needing surgery at some point in a patient’s life. Because there has not been much research done on the topic, this study examined the effects of preoperative narcotic use in patients who had an abdominal surgery for Crohn’s disease.

There were 1331 patients who received abdominal surgeries for Crohn’s disease between 1998 and 2014 in this retrospective study. Preoperative narcotic use, defined as electronic documentation of use of narcotics within the month before surgery, was identified in 267 of the patients. The end points studied were overall morbidity, length of stay in the hospital, and hospital readmission within 30 days of discharge.

The results showed that patients who had preoperative narcotic use had an average length of stay in the hospital of 11.2 days while those who did not use narcotics before the surgery had an average length of stay of 7.7 days. The results also showed that preoperative narcotic use was associated with an increased risk 30 day hospital readmission. A multivariable analysis was performed to show that preoperative narcotic use was an independent factor in both of these outcomes. Additionally, the risk of hospital readmission and longer length of stay was even higher when the use of preoperative narcotics was done in an outpatient setting rather than an inpatient setting.

The study concluded that preoperative narcotic use is associated with a longer length of stay in the hospital and a higher hospital readmission rate following abdominal surgeries for Crohn’s disease. It also added that, due to these findings, other options, like surgery, should be considered before narcotics for patients with Crohn’s disease. The fact that the use of narcotics as an outpatient was associated with a higher risk of adverse outcomes makes these findings more relevant to community pharmacists. The pharmacist has the potential to be an additional checkpoint for patients with Crohn’s disease who are starting to use narcotics. Knowing that preoperative narcotic use is associated with adverse postoperative outcomes could give pharmacists the opportunity to intervene and help investigate other treatment options before patients begin to use and rely on narcotics.

 

JAMA Surg. doi: 10.1001/jamasurg.2015.5558 (published February 24, 2016).

Natural Killer Cells and Liver Transplantation: Orchestrators of Rejection or Tolerance?

Rejection of the donor organ is a major concern in any type of transplantation, and this issue is usually addressed by the use of immunosuppressive medications. The lifelong use of immunosuppressive agents post-transplant puts patients at a higher risk for other diseases, infections, and, ultimately, mortality. Thus, reduced immunosuppression could be beneficial to patients in some ways.

This review article examines evidence that shows the relationship between natural killer cells and liver transplantation. Natural killer cells are a type of lymphocyte that play a role in antiviral and tumor immunity and make up 30-50% of lymphocytes in the liver. It is known that natural killer cells from recipients are important in rejection because they are a source of IFN-γ, which triggers T cell response and inflammation. However, studies have also shown that natural killer cells from donors may have a role in tolerance of transplanted organs. More studies on the role of donor natural killer cells in tolerance in liver transplantation have the potential to allow for a reduction in immunosuppression when transplanted livers have a larger number of natural killer cells.

Because reduced immunosuppression could lead to a reduced risk of mortality in transplant recipients, this is an important topic to investigate further. Changing immunosuppression protocols and methods in liver transplantation could dramatically affect pharmacists because they could become a more valuable resource in determining immunosuppressive medication regimens. As medication experts, pharmacists have the knowledge base and practice area to really determine the best immunosuppressive medications based on new findings on the relationships between medications and natural killer cells. As more research is conducted on the role of natural killer cells in tolerance and their interactions with immunosuppressive medications, the role of the pharmacist on the transplant team has the potential to really expand.

 

Am J Transplant. 2016; 16: 751-7.

Buprenorphine versus Methadone Treatment for Neonatal Abstinence Syndrome

Neonatal abstinence syndrome (NAS) is the heartbreaking condition in infants that results from maternal use of opioids during pregnancy. This condition is characterized by infants’ experiences of withdrawal symptoms. Illegal opioid pain relievers or heroin were used by more than 1% of pregnant women in 2011, but illicit drug use is not the only source of opioid use during pregnancy. Surprisingly, opioids were dispensed to over 14% of pregnant women between 2005 and 2011. Approximately 5.8 cases of NAS per 1000 live births occurred by 2012. As the opioid crisis continues and grows in our nation, it is becoming more important to study treatment options available for infants with NAS. The standard treatment is oral methadone and morphine. This study investigates the potential use of buprenorphine in treating NAS.

This retrospective cohort analysis performed in six hospitals in Southwest Ohio between 2012 and 2014 sought to compare the duration of opioid therapy and length of inpatient hospital stay in infants treated for NAS with the standard oral methadone treatment regimen versus sublingual buprenorphine-weaning protocol. At the six sites a total of 163 infants were treated with the standard 8-step methadone protocol, and at one site a total of 38 infants were treated with sublingual buprenorphine based on a 5-step protocol from another study. Buprenorphine dosing was weight-based and initiated at 4.4 μg/kg every 8 hours at a maximum daily dose of 39 μg/kg. Infants who had chronic intrauterine exposure to methadone were excluded from the buprenorphine treatment group and were treated with oral methadone.

The results of the study showed that patients who received buprenorphine had an average duration of treatment of 9.4 days and an average length of stay of 16.3 days while patients who received methadone had an average duration of treatment of 14 days and an average length of stay of 20.7 days. The were no adverse effects or increases in adjunct therapy with phenobarbital in the buprenorphine group compared to the methadone group. Additionally, buprenorphine may be safer than methadone because it has a ceiling effect on respiratory depression.

This study concluded that buprenorphine could be superior to methadone in the treatment of NAS in infants whose mothers did not use methadone. I found this article extremely interesting because I do not often think of the need to treat opioid dependence in infants, and it seems like much more research could be done on this topic. One of the authors of the study was a pharmacist, and I think that this area of practice has a lot of potential for pharmacist involvement. Pharmacists could play in important role in selecting treatment for NAS as well as determining drug dosing because it could be very different for this population and involves constantly changing doses in order to wean infants off of opioids.

 

J Pediatr. 2016; 170: 39-44.

Contextual Predictors of Injection Drug Use Among Black Adolescents and Adults in US Metropolitan Areas, 1993-2007

Illegal drug use has been and continues to be a problem in the United States, and part of solving this problem may be determining factors that influence illegal drug use. This study sought to determine whether there were contextual elements that could predict the use of injectable drugs by Black adolescents and adults in metropolitan areas. The study was longitudinal and was conducted from 1993-2007. It included data from 95 US metropolitan statistical areas (MSAs) and included individuals between 15 and 64 years old. Data on injection drug use (IDU), socioeconomic status, criminal justice activities, spending on social welfare, health, and policing, and history of Black uprisings was collected.

 

The results of the study showed that contextual factors can be predictive of IDU among Black adolescents and adults. Higher percentages of Black residents in MSAs was associated with less IDU by Black residents. Prevalence of Black IDU was also lower in areas with lower Black high-school dropout rates, history of Black uprisings, and higher Black income when White income was high. Higher public welfare spending was associated with higher prevalence of Black IDU. Urban renewal funding and incarceration rates were found to be unrelated to Black IDU prevalence.

 

While I was able to predict some of the contextual factors that were linked to IDU in this article, some were unknown to me and were found to have opposite effects from what I initially thought. For example, I would have guessed that a history of Black uprisings would lead to a higher prevalence of IDU. The article suggests that the true association may be due to the fact that uprisings actually often occurred in more economically stable Black communities, and more material resources and less social stress have protective effects on IDU. Contextual predictors like those determined in this study are interesting to me because they have the potential to play a role in the resolution to the problem of illegal drug use. Do you think that these same contextual predictors would apply to other forms of illegal drug use like prescription opioid abuse? Why or why not? And how do you think this information could be used to reduce illegal drug use?

 

Am J Public Health. 2016; 106 (3): 517-26.

Early Hospital Readmission After Simultaneous Pancreas-Kidney Transplantation

Transplant patients have a fairly high risk for early hospital readmission (EHR) after discharge, which has been linked to higher morbidity, mortality, and cost for hospitals and patients. Studies have been done to determine the risk of EHR for patients who receive kidney transplants, but this study is one of the first to look at factors contributing to EHRs following simultaneous pancreas-kidney transplantation (SPK). SPK is a form of treatment for diabetes and end stage renal disease.

The objective of this study was to determine the patient and center-level factors that contribute to the likelihood of EHR after SPK. The study was conducted nationally from 1999-2011 and included 3643 adult first-time SPK recipients whose primary insurance was Medicare Part A and B. Patient-level factors investigated included recipient and donor age, sex, race, and BMI as well as recipient comorbidities, length of stay for SPK, and year of transplant, and donor cause of death. Center-level factors investigated included total number of SPKs, average length of stay, percent of African American SPK patients, and median time to transplant. EHR was considered to be at least one hospital readmission within 30 days of discharge following SPK length of stay.

The study results showed that 55.5% of SPK recipients had at least one EHR and 23.1% of those were due to infections. Other major reasons for readmission included kidney/urinary tract disorders, alimentary tract disorders, pancreatic/hepatobiliary disorders, and electrolyte/nutritional disorders. Patient-level factors that were associated with an increased risk of EHR were younger recipients, African American donors, overweight donors, and length of stay. No center-level factors were found to affect the likelihood of EHR.

I found it particularly interesting that the study pointed out that younger patients may be more likely to have an EHR following SPK because young adults with type 1 diabetes may not be as compliant with their postoperative medication regimens as older adults. I think that this could be a great way to bring a pharmacist into this conversation about post-transplant EHRs. A pharmacist might be especially useful in helping patients to reach glycemic control and in managing immunosuppressive medications following SPK. In what other ways do you think a pharmacist may be able to contribute to lowering the risk of EHRs in SPK (or any type of transplant) recipients?

 

 

Am J Transplant. 2016; 16 (2): 541-549.

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.