Palatability of a novel oral formulation of prednisone in healthy young adults.

OBJECTIVES: Prednisone is a widely used anti-inflammatory for a variety of conditions. While oral liquid formulations of prednisone enable weight-based dosing, children frequently find them to be objectionable due to bitter taste. This limitation of prednisone can adversely impact patient acceptance and may result in non-compliance. Efforts to mask flavours often result in poorly controlled, heterogeneous particle distributions and can provide ineffective taste masking. The present work utilized a novel drug delivery technology developed by Orbis Biosciences, Inc., to create an oral taste-masked formulation of prednisone. METHODS: The study examined the palatability of Orbis' microsphere prednisone formulation in healthy young adults (n = 24). Four test articles were used in the study including a reference formulation (Roxanne Laboratories), a control and the test formulation (Orbis) prepared in two different ways. Study participants were randomized in a crossover design. KEY FINDINGS: Results indicated that the test prednisone formulation was indistinguishable from the control, and both were preferable to the reference formulation in every category of palatability assessed using a validated 9-point Hedonic Scale. The data also suggested that preparing the microsphere suspension immediately before administration results in the most ideal palatability properties. CONCLUSIONS: In conclusion, the novel microsphere formulation technology was effective in taste-masking prednisone.

Transesophageal Doppler measurement of renal arterial blood flow velocities and indices in children.

BACKGROUND: Doppler-derived renal blood flow indices have been used to assess renal pathologies. However, transesophageal ultrasonography (TEE) has not been previously used to assess these renal variables in pediatric patients. In this study, we (a) assessed whether TEE allows adequate visualization of the renal parenchyma and renal artery, and (b) evaluated the concordance of TEE Doppler-derived renal blood flow measurements/indices compared with a standard transabdominal renal ultrasound (TAU) in children. METHODS: This prospective cohort study enrolled 28 healthy children between the ages of 1 and 17 years without known renal dysfunction who were undergoing atrial septal defect device closure in the cardiac catheterization laboratory. TEE was used to obtain Doppler renal artery blood velocities (peak systolic velocity, end-diastolic velocity, mean diastolic velocity, resistive index, and pulsatility index), and these values were compared with measurements obtained by TAU. Concordance correlation coefficient (CCC) was used to determine clinically significant agreement between the 2 methods. The Bland-Altman plots were used to determine whether these 2 methods agree sufficiently to be used interchangeably. Statistical significance was accepted at P ≤ 0.05. RESULTS: Obtaining 2-dimensional images of kidney parenchyma and Doppler-derived measurements using TEE in children is feasible. There was statistically significant agreement between the 2 methods for all measurements. The CCC between the 2 imaging techniques was 0.91 for the pulsatility index and 0.66 for the resistive index. These coefficients were sensitive to outliers. When the highest and lowest data points were removed from the analysis, the CCC between the 2 imaging techniques was 0.62 for the pulsatility index and 0.50 for the resistive index. The 95% confidence interval (CI) for pulsatility index was 0.35 to 0.98 and for resistive index was 0.21 to 0.89. The Bland-Altman plots indicate good agreement between the 2 methods; for the pulsatility index, the limits of agreement were -0.80 to 0.53. The correlation of the size of the measurement and the mean difference in methods (-0.14; 95% CI = -0.28, 0.01) was not statistically significant (r = 0.31, P = 0.17). For the resistive index, the limits of agreement were -0.22 to 0.12. The correlation of the size of the measurement and the mean difference in methods (-0.05; 95% CI = -0.09, -0.01) was not statistically significant (r = 0.10, P = 0.65). CONCLUSION: This study confirms the feasibility of obtaining 2-dimensional images of kidney parenchyma and Doppler-derived measurements using TEE in children. Angle-independent TEE Doppler-derived indices show significant concordance with those derived by TAU. Further studies are required to assess whether this correlation holds true in the presence of renal pathology. This technique has the potential to help modulate intraoperative interventions based on their impact on renal variables and may prove helpful in the perioperative period for children at risk of acute kidney injury.

Evaluation of a local ICU sedation guideline on goal-directed administration of sedatives and analgesics.

PURPOSE: Sedatives and analgesics are commonly used in mechanically ventilated patients in the intensive care unit. Sedation guidelines have been shown to improve sedation management as well as various patient outcomes. The main objective was to evaluate adherence to a sedation guideline with both sedative prescribing and documentation of Richmond Agitation-Sedation Scale (RASS) scores. METHODS: In a retrospective chart review, data was collected on 111 medical intensive care unit patients mechanically ventilated via endotracheal tube for 12 hours or greater at Brigham and Women's Hospital. Fifty-seven patients were evaluated pre-guideline implementation and 54 patients were evaluated post-guideline. RESULTS: Significant increases were seen in the post-guideline group in goal-directed sedation with a patient-specific RASS goal in the sedation order: 21.3 vs 85.4% (P < 0.001), and mean number of sedation assessments per 24 hours using the RASS: 4.7 vs 11.4 (P < 0.001). Similarly, this group experienced a higher percentage of RASS scores at their sedation goal: 31.4 vs 44.1% (P < 0.001). No difference was seen in other clinical endpoints. CONCLUSION: Implementation and routine application of a hospital pain and sedation guideline was associated with significantly improved sedation metrics, such as goal-directed sedation, as well as frequency of sedation level assessment and documentation. An increase was observed in the time that post-guideline patients spent at or near their RASS goal.