Class of 2013 Abstract / Specific Aims: The objective of this study was to describe the failure rate of activation of medications that employ the ADD-Vantage medication delivery system in one community hospital, Tucson Medical Center (TMC). Methods: A daily, hospital-wide summary was generated identifying all patients currently receiving ADD-Vantage medications using the TMC electronic medical record system, Epic. Data collection occurred on arbitrary days and times from July 2012 to March 2013. Direct observation of a failure or a success in activation occurred by entering a patient’s room after the ADD-Vantage medication was administered by the nurse. Important data collected included: medication, frequency of administration, nursing unit, time of administration, administering nurse, the shift during which the nurse was working and whether or not the medication was or was not properly activated. Main Results: All medications utilizing the ADD-Vantage medication delivery system at TMC were analyzed. The rate of failure across 347 total samples collected on various days and times was 6.92%. Night shift had a higher rate of failure at 11.43% versus 6.41% for day shift (χ2 = 1.23). The General Surgery and Cardiac units of the hospital had the highest rates of failure with 18.18% and 15.38% respectively. Zosyn was improperly activated with greatest frequency with 12 total failures. Conclusion: No statistically significant difference was found between the rates of activation failure for those samples collected during nursing day shift versus night shift. The overall rates of activation failure suggest a significant opportunity for nursing education to improve outcomes.

Class of 2005 Abstract / Objectives: To determine if delivery of medications to an independent living facility increases patient adherence. Methods: Retrospective review of patient pharmacy refill records was completed using a data extraction form in order to calculate a number of days deviation from a projected refill date based on days supply. Data on the use of express pay, auto fill, and delivery service and payment type was collected as well as age and gender. Residents of The Fountains independent living facility were eligible to be included in this study if they had complete data in the pharmacy refill records for at least one scheduled maintenance medication taken for a continuous, three-month period. Results: There were 21 subjects in the delivery group and 18 in the pick-up group. Both groups were primarily women (76.2 percent and 61.1 percent respectively). Age was also similar (85.8 and 83.8, p=0.285). The delivery group had significantly more maintenance medications than the pick-up group (mean=2.8, SD=1.1 and mean=1.7, SD=1.1 respectively). Seven of the nine time deviations were greater for the pick-up group than for the delivery group (p= 0.09 for sign test). Implications: It appears that a delivery service can increase adherence, particularly in a population of advanced age.

京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第21048号 / 薬科博第91号 / 新制||薬科||10(附属図書館) / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 髙倉 喜信, 教授 山下 富義, 教授 小野 正博 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

This study demonstrates the direct delivery of plasmid gene constructs into spinal motor neurons utilizing retrograde axoplasmic transport. The plasmid vectors contained the Lac Z gene under the control of both the Rous sarcoma virus (RSV) and Simian virus (SV)40 promoters. β-Galactosidase expression was observed in α and γ motor neurons by histochemical staining following direct injection into the sciatic nerve or gastrocnemius muscle. The presence of LacZ gene constructs was confirmed by the polymerase chain reaction (PCR). The ability to introduce gene constructs into motor neurons allows for the study of gene regulation and permits the development of gene therapy strategies for motor neuron diseases including the spinal muscular atrophies (SMA) and amyotrophic lateral sclerosis (ALS).

No description available.

<p> Although successful in laboratory studies, field applications of in situ remediation of chlorinated solvents in groundwater have met with limited success. This is most often attributed to the inability to deliver the amendment evenly throughout the target zone, especially in low permeability and heterogeneous materials. The goal of this research was to employ a prototype of a novel delivery system to evenly deliver amendment across the depth and breadth of the subsurface in a cost-effective method. The research was conducted at 42 Voyager Court, Toronto, ON where concentrations of vinyl chloride in groundwater were in excess of Ontario Ministry of the Environment guidelines (O.Reg.153/04). The subsurface consisted of sandy and clayey silt fill underlain by sandy silt till.</p> <p> The delivery system comprised 29, 1/4" diameter, delivery points with small perforations along the length, installed in a fence perpendicular to groundwater flow, approximately 0.5 m upgradient of the area of concern. The delivery system used low flow rates (approximately 13 to 23% of total groundwater flow) and discrete delivery holes to deliver a potassium permanganate solution (approximately 40 g/L) amended with sodium bromide (approximately 0.8 g/L) across the depth of the subsurface. Fourteen multi-level monitoring wells, each with five sampling ports were installed to monitor the effectiveness.</p> <p> After six months of delivery, sample results indicated that oxidant demand hindered the ability of potassium permanganate to reach and degrade the vinyl chloride. However, elevated bromide concentrations were detected at all downgradient sampling ports within a 1.5 m distance. Thus, the delivery system was successful at delivering the amendment across the depth and breadth of the target area and achieving even delivery.</p> <p> Problems, typically leaks, were encountered with the delivery system design. Additional engineering would be required to improve the header system prior to commercializing this process. This would be a beneficial endeavor, as results of this work indicate that this passive delivery fence technique meets a real need in the remediation industry, which is the even distribution of amendment to target zones in the saturated subsurface, including zones of low permeability.</p> / Thesis / Master of Applied Science (MASc)

Lipid-based drug delivery systems (LBDDSs) are becoming an increasingly popular approach to improve the oral absorption of poorly-water soluble drugs. Several possible mechanisms have been proposed to explain the means by which LBDDSs act in vivo to enhance absorption. The goal of the current dissertation is to provide a better understanding of one proposed mechanism; the capability of lipoidal components in LBDDS formulations to create and maintain a drug in a supersaturated state under simulated GI conditions. Moreover, molecular details of equilibrium solubilization of a drug in a series of model lipid assemblies were examined. The results of these studies will aid formulators in choosing the optimal LBDDS to improve oral absorption of poorly water-soluble drugs. Time-dependent solubilization behavior of progesterone, 17β-estradiol and nifedipine in a simple model LBDDS composed of Polysorbate 80 was assessed employing the in vitro dynamic lipolysis model. The results illustrated the extent to which the supersaturated state was dependent on the extent of lipolysis of Polysorbate 80 and the initial drug concentration. Area-under-the curve-supersaturation was proposed as a means of quantifying the time-dependent extent of supersaturation in LBDDSs in simulated intestinal conditions. Concurrently, a series of model mixed micellar solutions, composed of Polysorbate 80 and oleic acid, were prepared to represent the lipid assemblies produced during the lipolysis experiments. The ability of these aggregates to solubilize progesterone, 17β-estradiol and nifedipine were evaluated and the aggregate/water partition coefficients were determined. The Treinor model was found to successfully fit the partition coefficients of the drugs in a range of mixed micelles. The equilibrium solubility of drugs in the mixed micelles was calculated and compared to that found under lipolytic conditions. The best agreement between calculated and experimental conditions was observed for nifedipine. These studies have established a foundation for the evaluation of time-dependent extent of supersaturation with more complex LBDDS formulations exposed to lipolytic conditions.

The objective of this thesis is to explore the design of operational processes in information-intensive service delivery systems. Empirical data is presented which builds upon existing literature within the Business Process Management (BPM) and Service Operations Management (SOM) disciplines. Adopting a theory building mode, the thesis concludes with the formulation of several research propositions which specify the design characteristics of the processes that provide the service concept to the customer. The research addresses a number of gaps in the literature. First, there is little empirical evidence concerning the relationship between the service concept, customer inputs, and process design. Second, service classification schemes promote homogeneous thinking in the design of service systems delivering diverse service concepts. Third, the BPM literature provides generic process design principles which offer limited theoretical insights into the design requirements of operational processes. Finally, there is a need for process design research in information-intensive service organisations. A research framework that integrates theoretical models addressing service process design is investigated using a single case study approach. Fieldwork was carried out over a sixteen-month period in a large electricity supplier in the UK. In contrast to the macro-orientation found within the literature, this study employs a more granular level of analysis to address the unique requirements of ‘service concept – processes’ pairs. This approach results in a number of important findings which, in several instances, are in contradiction to current thinking. First, the results empirically validate the theoretical relationship between service concept, customer inputs, and process design. Different service concepts lead to different process designs, and the more customised the service concept, the more the process is uniquely designed. Significant differences in the design of the individual processes that collectively provide the service concept to the customer are highlighted. The results also provide some new insights into the design of front office – back office activities as well as into the design characteristics of processes characterised by low customer contact. In addition, the study refutes the view that generic process design principles are universally applicable irrespective of the context in which the processes operate. Finally, the research findings show that a process-based view of service systems allows for heterogeneity; that is differences in the design of service delivery processes within the same organisation.

De nombreuses études ont montré l'intérêt thérapeutique de molécules dérivant des microARN (inhibiteurs ou analogues) en cancérologie. Cependant avant d'espérer en faire de futurs médicaments, il est indispensable d'élaborer des systèmes permettant leur délivrance préférentielle dans les cellules cancéreuses. Dans ce travail, nous avons développé deux plateformes innovantes basées sur les microARN : la première utilise les propriétés optiques des quantum dots (QD) et est destinée à l'imagerie des microARN ; la seconde repose sur la sérum albumine humaine (SAH) et a une finalité de délivrance ciblée de microARN. La mise en place de ces plateformes a nécessité la synthèse d'une petite chimiothèque de bioconjugués lipidiques dérivés des microARN (inhibiteurs ou analogues), le but étant d'exploiter l'effet hydrophobe pour les fixer à la surface des QD (ancrage hydrophobe dans la paroi lipidique des QD) et de la SAH (interaction avec les sites de liaison aux acides gras). Dans les deux cas, différentes études incluant des caractérisations physico-chimiques (MET, DLS), des expériences in vitro (SPR) et in cellulo (microscopie de fluorescence, criblage fonctionnel, RTqPCR) ont montré la potentialité de ces nouvelles plateformes. / Exploitation of gene-silencing is a very promising strategy in human therapeutics. Several engineered small non coding RNAs (inhibitors or mimics) are already in preclinical and clinical trials. However a key impediment to the wider success of these approaches remains the specific delivery of RNA-derived molecules into cancerous cells. This work aimed at developing two innovative microRNA-based plateforms : the first one relying on quantum dots (QD) is dedicated to microRNA imaging and the second one based on human serum albumin (HSA) represents a new targeted delivery system. The implementation of both plateforms required the synthesis of a small library of microRNA derived lipidic bioconjugates (inhibitors or mimics), the aim being to exploit the hydrophobic effect for their loading on QD (hydrophobic anchoring in the hydrophobic QD surface) and on HSA (interaction with fatty acid binding sites). In both cases, different studies including physico-chemical caracterizations (TEM, DLS), in vitro (SPR) and in cellulo experiments (fluorescence microscopy, functional screening, RTqPCR) demonstrated the great promises held by these new plateforms.

This dissertation discusses anti-HIV-1 microbicide research. In particular, it concentrates on microbicide formulation and delivery. Microbicides are anti-HIV-1 agents that when applied in the human vagina or rectum may prevent sexual HIV-1 transmission. Although most of the anti-HIV-1 agents being developed as microbicides are active in vitro, they have proved to be ineffective in vivo. A review of microbicide development over the last decade expounds the view that unsatisfactory microbicide failures may be a result of inefficient delivery systems employed. Thus, necessitating a thorough scientific qualitative and quantitative investigation of important aspects involved in HIV-1 transmission as a prerequisite for microbicide development. In this dissertation it is postulated that intravaginal targeting of HIV-1 increases the chances of microbicide success, wherein vaginal micro-environmental factors including pH would be maintained at HIV-1 prohibitive acidic levels to ward off other sexually transmitted diseases which compromise vaginal epithelial barrier properties. Furthermore, targeting early stages of the HIV-1 infection accompanied by computation and delivery of appropriate microbicide quantities could result in an effective microbicide formulation. In an effort to address microbicide formulation challenges, an intravaginal delivery system able to deliver anti-HIV-1 agents (zidovudine and BP36) over 28 days was formulated. This delivery system is a caplet-shaped composite system comprising zidovudine (AZT) and BP36-loaded pectin-mucin-polyethylene glycol submicrospheres embedded within a poly(D,L-lactide), magnesium stearate, polyvinyl acetate/polyvinylpyrolidone (Kollidon® SR) and poly(acrylic acid) based polymeric caplet matrix. The delivery system was tested in vitro and in vivo in the pig model. X-ray imaging illustrated the delivery system swelling and its matrix contrast fading over time as vaginal fluid permeated the matrix’s core. Plasma, vaginal fluid and tissue drug was detected and quantified using ultra performance liquid chromatography-tandem photodiode array detector. AZT plasma and vaginal fluid concentrations measured on days; 3, 7, 14, 21 and 28 decreased gradually with time. Vaginal tissue AZT concentrations (after 28 days) were higher than plasma AZT concentrations and were in the same range as vaginal fluid AZT concentrations. The herbal extract, BP36, was detected in plasma, vaginal fluid and tissue but was only qualitatively analysed due to its lack of standardization. Histopathological analysis of excised vaginal tissue revealed different scores of abnormalities comprising mild to moderate epithelial proliferation and exocytosis, subepithelial leukocyte influx, perivascular cell cuffing and isolated epithelial erosion, stromal fibrosis and isolated tissue necrosis.