The association between timely opioid administration and hospitalization in children with sickle cell disease presenting to the emergency department in acute pain.

INTRODUCTION: The National Heart, Lung, and Blood Institute guidelines for sickle cell disease (SCD) pain crisis management recommend opioids within 60 minutes of emergency department (ED) registration and every 30 minutes thereafter until acute pain is managed. These guidelines are based on expert opinion without published, supporting data. OBJECTIVE: To evaluate the association between timely ED opioid administration and hospitalization rates in children with SCD. METHODS: Retrospective cohort of children presenting to a children's hospital ED with SCD pain between January 1, 2014, and April 30, 2018. Visits were extracted using ICD codes, chief complaints, and receipt of at least one opioid, and then reviewed to confirm the visit was an uncomplicated pain crisis. The primary outcome was hospitalization, yes or no. Generalized estimating equations were used to determine adjusted odds of hospitalization for the timely administration of initial and second doses of opioids. RESULTS: Of the 902 eligible visits, 368 (40.8%) resulted in hospitalization. The mean (SD) age was 11.9 (± 5.2) years. The first opioid was administered within 60 minutes of arrival in 601 (66.6%) visits. The second opioid was administered within 30 minutes of the first in 84 (12.3%) visits. Receipt of the first opioid within 60 minutes of arrival was not associated with decreased hospitalization (1.30 [0.96-1.76]). However, receipt of the second dose within 30 minutes of the first was associated with decreased hospitalization (0.56 [0.33-0.94]). CONCLUSION: This study suggests an association between children with SCD receiving a second dose within 30 minutes of the first opioid dose and decreased hospitalizations.

Noradrenergic receptor modulation influences the acoustic parameters of pro-social rat ultrasonic vocalizations.

Rats produce high rates of ultrasonic vocalizations (USVs) in social situations; these vocalizations are influenced by multiple neurotransmitter systems. Norepinephrine (NE) plays a significant role in vocalization biology; however, the contribution of NE to normal, prosocial vocal control has not been well established in the rat. To address this, we used NE adrenoceptor agonists (Cirazoline, Clonidine) and antagonists (Prozasin, Atipamezole, Propranolol) to quantify the contribution of specific alpha-1, alpha-2, and beta NE receptors to USV parameters in male Long Evans rats during seminaturalistic calling. We found that multiple USV acoustic variables (intensity, bandwidth, duration, peak frequency, and call profile) are modified by alterations in NE signaling. Very generally, agents that increased NE neurotransmission (Atipamezole) or activated alpha-1 receptors (Cirazoline), led to an increase in intensity and duration, respectively. Agents that decreased NE neurotransmission (Clonidine) or blocked alpha-1 receptors (Prazosin) reduced call rate, intensity, and bandwidth. However, the beta-receptor antagonist, Propranolol, was associated with increased call rate, duration, and intensity. Limb motor behaviors were largely unaffected by any drug, with the exception of Clonidine. Higher doses of Clonidine significantly reduced gross motor, grooming, and feeding behavior. These results confirm the involvement of NE transmission in vocal control in the rat, and suggest that this USV model is useful for studying the neuropharmacology of behavioral measures that may have implications for disease states, such as Parkinson's disease. (PsycINFO Database Record

Characterization of early-onset motor deficits in the Pink1-/- mouse model of Parkinson disease.

In Parkinson disease (PD), a complex neurodegenerative disorder that affects nearly 10 million people worldwide, motor skills are significantly impaired. However, onset and progression of motor deficits and the neural correlates of these deficits are poorly understood. We used a genetic mouse model of PD (Pink1-/-), with phenotypic similarities to human PD, to investigate the manifestation of early-onset sensorimotor deficits. We hypothesized this mouse model would show early vocalization and gross motor dysfunction that would be progressive in nature. Pink1-/- mice, compared to wild type (WT) controls, were evaluated at 2, 3, 4, 5, and 6 months of age. To quantify deficit progression, ultrasonic vocalizations and spontaneous locomotor activity (cylinder test and pole test) were analyzed. Although somewhat variable, in general, Pink1-/- mice produced significantly more simple calls with reduced intensity as well as a larger percentage of cycle calls compared to WT counterparts. However, there were no significant differences in duration, bandwidth, or peak frequency for any of the ultrasonic call types between genotypes. Pink1-/- mice showed a significant impairment in limb motor skills with fewer hindlimb steps, forelimb steps, and rears and lands in the cylinder test compared to WT. Additionally, Pink1-/- mice took significantly longer to turn and traverse during the pole test. Immunohistochemical staining showed no significant difference in the number of tyrosine hydroxylase (TH) positive cells in the substantia nigra or density of TH staining in the striatum between genotypes. These data suggest the Pink1-/- mouse model may be instrumental in defining early motor biomarkers of PD in the absence of nigrostriatal dopamine loss.