No description available.

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A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Currently few studies have investigated the accuracy of using transcutaneous bilirubinometry after phototherapy especially in the outpatient setting. The purpose of this study was to evaluate the accuracy of transcutaneous bilirubin measurements (TCB) after phototherapy for neonates with jaundice. At the Maricopa Integrated Health System, neonates who undergo phototherapy for hyperbilirubinemia come in for outpatient follow‐up at the Comprehensive Health Center following their discharge. For those neonates, current protocol calls for serum bilirubin (TSB) to be measured to properly monitor bilirubin levels, however transcutaneous measurements were made and recorded as well. In this study, we compared the values of total serum bilirubin and transcutaneous bilirubin in jaundiced neonates who underwent phototherapy. From October 2013‐April 2015, a total 67 healthy infants were seen in the Pediatric Clinic who had received phototherapy in our hospital, only 36 (54%) of those met minimum data criteria to be included in the study. The absolute difference between mean serum bilirubin and transcutaneous bilirubinometry in healthy outpatient newborns who received inpatient phototherapy was 0.4 and is clinically insignificant. The average time from hospital discharge to return to clinic was 47 hours. We conclude that for the outpatient physician, transcutaneous bilirubinometry can be used following phototherapy, which facilitates faster, more convenient, and painless follow‐up visits.

MMed, Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, 2006

Class of 2005 Abstract / Objectives: First, to evaluate five recent gentamicin dosing protocols that are specific for neonates and determine how frequently each protocol yields desirable peak and trough concentrations. Second, to make our evaluation more robust, we included AUC as one of the pharmacokinetic parameters and compared it to traditional parameters. Finally, to evaluate a fixed dosing protocol (3 mg/kg Q24-hours) that is currently being used at one Arizona hospital (UMC). Methods: This retrospective evaluation involved datasets from three independent sources. Dataset 1 was from a previously published study, while datasets 2 and 3 were derived for this study. Datasets 1 and 2 were pooled to evaluate the five dosing protocols, while dataset 3 was used to evaluate the fixed dosing protocol used at UMC. For all subjects, demographic and laboratory data was obtained from hospital databases or charts. The data collected was used to construct pharmacokinetic values, which in turn were used in simulations with the five protocols. Dataset 3 was evaluated as a whole for frequency of desired peaks and troughs, then for subsets based on weight, gestational age, and Apgar scores. Results: Of the five evaluated, the Avent protocol yielded the fewest potentially toxic troughs. The Murphy-Carter protocol stood out in that it was the easiest to use, most universally applicable, and it yielded only slightly fewer desired troughs then the Avent protocol. AUC values proved to be a novel and exceptionally useful tool in evaluating the dosing protocols. The fixed dosing protocol used at UMC was shown to consistently produce favorable trough concentrations as a whole as well as in our subset analyses. Implications: The multitude of dosing protocols that have been offered can create confusion among health care professionals and lead to discrepancies in dosing. The primary goal of any of these protocols is to minimize the risk of toxicity while avoiding subtherapeutic doses. A dosing protocol that can consistently meet these criterion, yet offer simplicity and wide applicability, then we can come that much closer to a universal standard.

No description available.

Whooping cough is a common childhood disease caused by infection with the bacteria Bordetella pertussis or Bordetella parapertussis. Although previously considered under control within developed countries due to widespread vaccination, whooping cough has undergone a resurgence in many developed countries, with recent outbreaks underscoring the need for new and more effective vaccines. Most crucially, there is a need for vaccines that can be administered during the neonatal period, to protect infants at their most susceptible, and vaccines that will provide long-lasting protection. Due to the functional differences of the neonatal immune system as compared to the adult, there are specific difficulties that must be overcome when attempting to create a vaccine that will be effective in the neonate. The objective of the current research was to examine the immunogenicity of several adjuvants, including CpG ODN, IDRP, and PP, in order to design a combined novel adjuvant platform that could be used with our pertussis vaccine antigen, PTd. After selection of each adjuvant component, we tested the ability of various adjuvant formulations to induce Th1 and Th2 humoral responses in both adult and neonatal mice. We found that a 1:2:1 ratio of CpG ODN: IDRP: PP was most effective, and that pre-complexation of the IDRP and CpG ODN components induced significantly higher Th1 (IgG2a) antibody titres than non-complexed vaccines. Our vaccine platform induced strong Th1 and Th2 antibody titres in both adult and neonatal BALB/c mice, with the immune response being of a mixed Th1/Th2 type. The Th1 type humoral response to our vaccine platform was significantly higher than that seen using current commercial vaccines such as Quadracel®, or when using the standard vaccine adjuvant alum. This Th1 antibody response was extremely long-lasting, with strong IgG2a titres being found up to 2 years post-vaccination. When examining the cell-mediated immune response in adult and neonatal BALB/c mice, a strong secretory IFN-g (Th1) response was present post-vaccination in the splenocytes of platform-vaccinated mice, with a large number of IFN-g secreting cells present. The IL-5 (Th2) response was found to be decreased in mice that received our novel vaccine as compared to mice vaccinated with Quadracel®, with no detectable cytokine secreted by stimulated splenocytes in vitro, and few to no IL-5 secreting cells visible through ELISPOT. To further improve our vaccine, a second antigen, pertactin (PRN), was added to the formulation. Upon live bacterial challenge, mice that received the two-antigen vaccine were completely protected against infection, and showed strong humoral response. This full protection and clearance was superior to the results seen using Quadracel®. Finally, the variability and cell-recruitment functions of the adjuvant platform were examined. The adjuvant platform successfully induced a strong mixed Th1 and Th2 humoral response when combined with the vaccine antigen HBsAg, with a significant increase in the Th1 (IgG2a) antibody response. Replacing the CpG ODN component of the adjuvant platform with Poly I:C through and using various immunization routes also resulted in an induction of IgG2a titres. Thus we have developed a novel vaccine formulation against B.pertussis that induces strong humoral and cell-mediated immune responses in both adult and neonatal mice, with these responses being both long-lasting and protective against infection. Our novel adjuvant platform itself has been shown to be adaptable for use with other vaccine antigens and through several routes of administration, and there is the possibility of adjusting the components while maintaining efficacy.

Class of 2007 Abstract / Objectives: To create a nomogram that can accurately predict dosing intervals for aminoglycoside dosing in neonates based on one concentration measurement. Methods: Pooled pharmacokinetic data from previous studies were used (n=341) to create a nomogram that would accurately predict dosing intervals for aminoglycosides. The population value for volume of distribution (0.45 L/kg) was used to formulate a nomogram to select a dosing interval for neonates that would achieve a trough concentration of < 0.5 mg/L one hour prior to the next scheduled dose. The fixed dose of 4 mg/kg was used to simulate concentration elimination profiles all neonates in the study group. The data from the study group elimination profile was then compared against the nomogram and evaluated for the number of correct dosing intervals the nomogram predicted from hour 6 to 22 at 1 hour intervals. The trough concentration cutoff was < 0.5 mg/L with neonates not achieving this concentration prior to the next dose to be deemed dosed incorrectly. The nomogram was considered to have failed at any time point where the nomogram indicated an interval that would not have achieved the desired trough concentration of < 0.5 mg/L or if the interval chosen by the nomogram was longer then necessary. Results: The simulated data from the test group showed that from 15 to 21 hours post infusion 81.0 to 92.1% of neonates had the correct interval predicted by the nomogram. Greater accuracy was achieved the longer time that elapsed before a concentration is drawn, with the greatest accuracy (92.1%) at 21 hours post infusion. However, this was close to the next dose recommending a concentration draw time at 18 hours post infusion to maximize the combination of accuracy and time remaining before the next scheduled dose. This gives the lab time to report the concentration before the next dose is scheduled and achieves an accuracy rate of 87.6%. Conclusions: The use of this nomogram is a valid tool to predict dosing intervals for aminoglycosides in neonates and can aid in saving hospital resources by needing only one concentration measurement to determine dosing interval.