Thesis (Ph.D.) -- University of Rhode Island, 2009. / Typescript. Includes bibliographical references (leaves 266-298).

Includes bibliographical references and index.

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 138-152).

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 177-200).

Bakgrund: Vårdrelaterade infektioner är vanliga och leder till långa vårdtider, lidande för patienterna och höga kostnader för sjukvården. Målet med den preoperativa duschen med klorhexidintvål, byte av kläder och sänglakan efter duschen är att minska de negativa konsekvenserna. Det blir vanligare att preoperativa förberedelser görs i det egna hemmet eller på patienthotell, som en slags egenvård, för att sedan läggas in på preoperativ avdelning för resterande preoperativa förberedelser. För att detta ska lyckas krävs det relevant information från vårdpersonal och sjuksköterskorna har ett stort ansvar och plikt att förse patienterna med nödvändig information. Syfte: Att belysa hur patienter upplevde informationen om och genomförandet av preoperativa förberedelser i hemmet eller på patienthotell. Metod: En empirisk kvalitativ intervjustudie med semistrukturerade intervjuer. Materialet analyserades enligt Granheim och Lundmans beskrivning av innehållsanalys på manifest nivå. Urvalet genomfördes ändamålsenligt. Deltagarna i studien bestod av 13 patienter från en preoperativ avdelning i Mellansverige. Resultat: Deltagarna var övergripande nöjda med den preoperativa informationen och att utföra förberedelserna i hemmet eller på patienthotell. Individuella faktorer påverkade upplevelserna av den preoperativa informationen och beroende på individens förutsättningar varierade upplevelserna av de preoperativa förberedelser i hemmet eller på patienthotellet. Slutsats: Större delen av patienterna upplevde att den preoperativa informationen och att utföra de preoperativa förberedelserna i hemmet eller på patienthotell var positivt. Vissa faktorer gjorde upplevelserna negativa, dessa faktorer var individuella. Resultatet anses skapa större patientförståelse och belyser positiva och negativa delar av den preoperativa vården. / Background: Nosocomial infections are common and lead to long hospital stays and suffering for patients beside high costs for hospitals. The aim of preoperative shower with chlorhexidine soap, change of clothes and bed sheets after the shower is to reduce this. It is common that patients conduct the preoperative preparations in their own home or at a patient hotel, as a kind of self-care, then they are admitted to the preoperative ward for the remaining preoperative preparations. For the self-care to succeed they need relevant information from health professionals and nurses have a responsibility and duty to provide patients with necessary information. Aim: The aim of the study was to highlight patients' experiences about the preoperative information and the implementation of the preoperative preparations in their own home or at a patient hotel. Method: An empirical qualitative study with semi-structured interviews. The material was analysed according to Graneheim and Lundman's qualitative manifest content analysis. Patients were included through a purposive sampling and 13 patients from a preoperative ward in central Sweden participated in the study. Results: The participants were overall satisfied with the preoperative information and carrying out the preparations at home or in a patient hotel. Individual factors affected the experience of the preoperative information and due to individual circumstances the experiences of preoperative preparation at home or at a patient hotel varied. Conclusion: Most of the patients felt that the preoperative information and the implementation of the preoperative preparation at home or in a patient hotel were positive. Certain factors were experienced negative, these factors were individual. Based on the results of this study greater patient understanding is created and it highlights the positive and negative elements in the preoperative self-care.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic cell death in the substantia nigra pars compacta (SNc) and dopamine (DA) depletion in the striatum. Current pharmacological treatments are aimed at the replacement of striatal DA via the administration of levodopa. While this therapy is beneficial initially, long-term treatment is associated with significant side effects, and disease progression continues. The present experiments investigate neuroprotective and neurotransplantation strategies as alternatives to palliative pharmacologic treatments. The optimal therapeutic approach to neurodegenerative diseases would be to protect against cell death and prevent disease progression. PD is well-suited for such neuroprotective strategies as primarily one cell population is affected in this disorder. Neurotrophic factors (NTFs) have been identified which support dopaminergic neuronal survival in vitro. In the present studies, the neuroprotective effects of the neurotrophin brain-derived neurotrophic factor (BDNF) have been evaluated in a 1-methyl-4-phenylpyridinium (MPP+) model of substantia nigra (SN) degeneration. BDNF-secreting fibroblasts were implanted dorsal to the SN prior to the infusion of the mitochondrial complex I inhibitor MPP+. Subsequent histological analysis demonstrated that BDNF is able to attenuate MPP+ induced dopaminergic cell loss in the SNc. Moreover, neurochemical evaluation demonstrated that BDNF is able to enhance DA levels in the remaining SN neurons in this same paradigm. The cause of cell death in neurodegenerative diseases likely involves the interaction of mitochondrial impairment, excitotoxicity, and oxidative stress. In order to evaluate the mechanism of NTF-mediated protection, the ability of nerve growth factor (NGF) to attenuate the production of the oxidant peroxynitrite was evaluated in a model of mitochondrial impairment. NGF was found to decrease the production of 3-nitrotyrosine, the product of peroxynitrite mediated tyrosine nitration. Thus, NTF-mediated neuroprotection may act in part by decreasing reactive oxygen species and oxidative stress. At present, neuroprotective therapies are not clinically available. An alternate therapeutic approach to PD is the replacement of striatal DA and reconstruction of synaptic circuitry via the intrastriatal transplantation of fetal dopaminergic neurons. Current transplantation protocols using human fetal tissue are constrained by limited tissue availability. In order to investigate an alternate cell source for the treatment of PD, fetal porcine dopaminergic neurons were implanted into the DA depleted striatum of 6-OHDA lesioned rats. Amphetamine-induced rotational recovery was monitored, and graft survival was evaluated 19 weeks after grafting. In immunosuppressed rats, porcine dopaminergic neurons were found to attenuate rotational deficits and extensively reinnervate the host striatum. The neuroprotective effects of BDNF suggest that NTFs may be important mediators of dopaminergic neuronal survival and function in the adult brain. However, several conditions including appropriate dosage and delivery need to be determined before clinical applications may be achieved. As an alternative to neuroprotection, neurotransplantation not only restores striatal DA but also reconstructs the synaptic circuitry of the basal ganglia. The finding that porcine dopaminergic neurons survive with in adult host brain, reinnervate the DA depleted striatum, and mediate functional recovery suggests that porcine DA neurons may serve as an alternate cell source for transplantation in PD.

A vigabatrina (VGB) é um fármaco anticonvulsivante que apresenta apenas a forma farmacêutica sólida disponível para uso. Na área hospitalar, devido à ausência de medicamentos na forma farmacêutica líquida, são preparadas derivações a partir de comprimidos e cápsulas para adequar a administração da dose prescrita. No entanto, a falta de estudos de estabilidade podem comprometer a eficácia e segurança destas derivações. O objetivo deste trabalho foi analisar a estabilidade química de derivações de comprimidos de vigabatrina em condições de armazenamento sob diferentes temperaturas e variações na embalagem utilizada. A análise das derivações de VGB foi realizada através de cromatografia líquida de alta eficiência (CLAE). O método descrito na Farmacopeia Britânica (2016) foi covalidado quanto a especificidade, linearidade, precisão e exatidão. Amostras de derivação de VGB foram preparadas em triplicata e acondicionadas em frascos de vidro e de PET âmbar. Após, foram armazenadas sob três diferentes condições de temperatura: temperatura ambiente (15 a 30 °C), sob refrigeração (2 a 8 °C) e em estufa (40 °C). Foram coletadas amostras armazenadas nas diferentes embalagens a cada 7 dias, por um período de 35 dias para as amostras conservadas em temperatura ambiente e refrigerada. O mesmo procedimento foi realizado para as amostras conservadas em estufa, porém por um período de 28 dias Também foi analisado o pH das amostras em cada tempo de coleta. As derivações de VGB foram analisadas por CLAE e apresentaram variação dentro dos limites preconizados pela Farmacopeia Britânica 2016, até 21 dias para frascos de vidro e de PET âmbar para as temperaturas ambiente e refrigerada. As amostras de VGB conservadas em estufa, apresentaram redução acima de 10% após 7 dias de estudo. A menor variação de pH ocorreu em frasco de vidro âmbar armazenado sob refrigeração. O resultado deste estudo serve de referência no preparo de derivações de VGB para uso hospitalar, pois apresentou intervalo de tempo confiável e condições de armazenamento adequadas para sua utilização. Desta forma, os pacientes pediátricos que utilizam doses fracionadas ou pacientes em uso de sondas nasogástricas terão as derivações adequadamente preparadas, reduzindo o risco de erros de diluição e contaminação microbiológica, melhorando a eficácia e segurança terapêutica. / Vigabatrin (VGB) is an anticonvulsant drug that has only solid dosage form available for use. In hospital, due to lack of medicines in liquid dosage form, extemporaneous preparations are prepared from tablets and capsules to adapt the administration of the prescribed dose. However, the lack of stability studies may compromise the efficacy and safety of these preparations. The aim of this study was to analyze the chemical stability of VGB extemporaneous preparation from tablets at storage conditions in different temperatures and variations of packaging used. The analysis of VGB extemporaneous preparations were performed by high-performance liquid chromatography (HPLC). The method described in British Pharmacopoeia (2016) was co-validated for specificity, linearity, precision and accuracy. VGB extemporaneous preparations were prepared in triplicate and placed in amber glass and PET bottles, which were stored under three different conditions: at room temperature (15 to 30 °C), under refrigeration (2 to 8 °C), and oven (40 °C). Samples of preparations stored at room temperature and refrigeration were collected every 7 days along 35 days. The same was done for solutions kept at 40 °C, but for a period of 28 days. It was also analyzed the preparations pH for each sampling time VGB extemporaneous preparations were analyzed by HPLC and demonstrated variations within the limits of British Pharmacopoeia (2016) up to 21 days in amber glass and PET bottles at room and refrigerated temperatures. VGB content for preparations kept in oven decreased above 10% after 7 days of study. The lowest pH change occurred in amber glass bottle stored under refrigeration. Results of this study can be applied as a reference for VGB extemporaneous preparation in hospital, once it was demonstrated the reliability of storage time interval and proper conditions for the use. Thus, pediatric patients with fractionated doses or patients using nasogastric probe will have adequately prepared extemporaneous preparations, reducing the risk of dilution errors and microbiological contamination.

Os eventos adversos a medicamentos são comuns e provavelmente irão ocorrer em qualquer sistema, entretanto, é essencial identificar suas causas e tentar minimizar os riscos visando à segurança do paciente. O objetivo desse estudo foi analisar os eventos adversos a medicamentos em um hospital público do estado do Amazonas, com base nos relatos da equipe de enfermagem e propor estratégias à instituição para otimizar o sistema de medicamentos para a segurança do paciente. Um estudo do tipo descritivo, adotando-se a Técnica do Incidente Crítico como norteadora dos procedimentos metodológicos foi realizado com 15 enfermeiros, 09 auxiliares e 44 técnicos de enfermagem de um hospital de ensino de Manaus-AM. A análise dos dados constou da identificação e agrupamento das situações, comportamentos e consequências. A maioria dos profissionais entrevistados era do sexo feminino (89,7%), predominando a classe de idade de 31 a 35 anos (30,9%). Os resultados foram agrupados e categorizados em 47 situações, correspondentes a nove tipos de erros de medicação. Dos tipos de erros identificados pela equipe de enfermagem, os erros de diluição (23,4%), dose (14,9%), medicamentos não autorizados (14,9%), erro de via de administração (10,6%) e erro de paciente (8,5%) foram os mais frequentes. Com relação às categorias de comportamentos, estes foram distribuídos em função da percepção e comunicação do erro (36) e entre as consequências identificadas no estudo (103), 47 eram relacionadas aos pacientes e 56 aos profissionais de enfermagem. Os resultados apresentados indicam a necessidade de tomada imediata de iniciativas que minimizem essas situações e previna a ocorrência de futuros eventos adversos a medicamentos. / Adverse drug events are common and will probably occur in any system, however, it is essential to identify their causes and try to minimize the risks to patients\' safety. This descriptive study aimed to analyze adverse drug events at a public hospital in the state of Amazonas, based on the reports of the nursing team. The goal was to propose strategies for the institution to optimize the medication system for patient safety. The Critical Incident Technique guided the methodological procedures, carried out with 15 nurses, 09 nursing auxiliaries and 44 nursing technicians from a teaching hospital in Manaus, state of Amazonas. Data analysis consisted of identifying and grouping situations, behaviors and consequences. Most of the interviewed professionals were female (89.7%) from the age group of 31 to 35 (30.9%) years. Results of the studies were grouped and categorized into 47 situations, corresponding to nine types of medication errors. Of the types of errors identified by the nursing team, dilution errors (23.4%), dosing errors (14.9%), unauthorized medication (14.9%), wrong administration route (10.6%) and mistaken patient (8.5%) were the most frequent. The categories of behavior were distributed according to the perception and communication of error (36) and among the consequences identified in the study (103), of which 47 were related to patients and 56 to nursing professionals. The results indicate the need for immediate initiatives that minimize these situations and prevent the occurrence of future adverse drug events.

Depuis ces dernières décennies, l'administration ophtalmique est devenue une voie privilégiée des molécules en vue d'une action locale. La sécurité, l'efficacité et l'acceptabilité de ces médicaments imposent une formulation stérile et facilement applicable pour l'amélioration de l'observance du patient. L'objectif de ce travail a été de développer une forme ophtalmique topique efficace, facilement applicable et contenant un principe actif (PA) d'intérêt. Les études d'encapsulation du PA dans des particules de polymères en vue de sa protection mettent en évidence la difficulté de formuler des vecteurs avec un PA hydrosoluble. Son instabilité en solution aqueuse a été démontrée lors des études de stabilité et a orienté le choix galénique vers des préparations semi-solides. L'absence, ou la faible quantité d'eau présente, améliore la stabilité du PA. L'association des cyclodextrines dans la formulation montre une nette stabilisation du PA dans les préparations semi-solides. Les études de caractérisation de ces formes mettent en évidence la stabilité du PA dans une pommade hydrophobe et dans une émulsion en présence de cyclodextrine. De plus, les essais de microbiologie démontrent l'intérêt de l'utilisation d'une émulsion dans l'efficacité de la forme pharmaceutique contre Staphylococcus aureus. Les formes ophtalmiques mise au point présentent un intérêt majeur dans le traitement d'infections oculaires localisées en remplacement des thérapeutiques actuellement sur le marché / Over the last few decades, ophthalmic administration has become a preferred route for molecules for local action. The safety, efficacy and acceptability of these drugs require a sterile and easily applicable formulation for improved patient compliance. The objective of this work was to develop an effective, easily applicable topical ophthalmic form containing a drug of interest. Studies of the encapsulation of API in polymer particles for protection show the difficulty of formulating vectors with a water-soluble API. The instability of the drug in aqueous solution has been demonstrated in stability studies and guided galenic choice to semi-solid preparations. The absence, or small amount of water, improves the stability of the API. The association of cyclodextrins in the formulation shows a marked stabilization of the drug in semi-solid preparations. Characterization studies of these forms demonstrate the stability of the drug in a hydrophobic ointment and in an emulsion in the presence of cyclodextrin. Moreover, microbiological tests demonstrate the advantage of using an emulsion in the efficacy of the pharmaceutical form against Staphylococcus aureus. The ophthalmic forms developed are major interest in the treatment of localized eye infections in place of the therapeutics currently on the market

A vigabatrina (VGB) é um fármaco anticonvulsivante que apresenta apenas a forma farmacêutica sólida disponível para uso. Na área hospitalar, devido à ausência de medicamentos na forma farmacêutica líquida, são preparadas derivações a partir de comprimidos e cápsulas para adequar a administração da dose prescrita. No entanto, a falta de estudos de estabilidade podem comprometer a eficácia e segurança destas derivações. O objetivo deste trabalho foi analisar a estabilidade química de derivações de comprimidos de vigabatrina em condições de armazenamento sob diferentes temperaturas e variações na embalagem utilizada. A análise das derivações de VGB foi realizada através de cromatografia líquida de alta eficiência (CLAE). O método descrito na Farmacopeia Britânica (2016) foi covalidado quanto a especificidade, linearidade, precisão e exatidão. Amostras de derivação de VGB foram preparadas em triplicata e acondicionadas em frascos de vidro e de PET âmbar. Após, foram armazenadas sob três diferentes condições de temperatura: temperatura ambiente (15 a 30 °C), sob refrigeração (2 a 8 °C) e em estufa (40 °C). Foram coletadas amostras armazenadas nas diferentes embalagens a cada 7 dias, por um período de 35 dias para as amostras conservadas em temperatura ambiente e refrigerada. O mesmo procedimento foi realizado para as amostras conservadas em estufa, porém por um período de 28 dias Também foi analisado o pH das amostras em cada tempo de coleta. As derivações de VGB foram analisadas por CLAE e apresentaram variação dentro dos limites preconizados pela Farmacopeia Britânica 2016, até 21 dias para frascos de vidro e de PET âmbar para as temperaturas ambiente e refrigerada. As amostras de VGB conservadas em estufa, apresentaram redução acima de 10% após 7 dias de estudo. A menor variação de pH ocorreu em frasco de vidro âmbar armazenado sob refrigeração. O resultado deste estudo serve de referência no preparo de derivações de VGB para uso hospitalar, pois apresentou intervalo de tempo confiável e condições de armazenamento adequadas para sua utilização. Desta forma, os pacientes pediátricos que utilizam doses fracionadas ou pacientes em uso de sondas nasogástricas terão as derivações adequadamente preparadas, reduzindo o risco de erros de diluição e contaminação microbiológica, melhorando a eficácia e segurança terapêutica. / Vigabatrin (VGB) is an anticonvulsant drug that has only solid dosage form available for use. In hospital, due to lack of medicines in liquid dosage form, extemporaneous preparations are prepared from tablets and capsules to adapt the administration of the prescribed dose. However, the lack of stability studies may compromise the efficacy and safety of these preparations. The aim of this study was to analyze the chemical stability of VGB extemporaneous preparation from tablets at storage conditions in different temperatures and variations of packaging used. The analysis of VGB extemporaneous preparations were performed by high-performance liquid chromatography (HPLC). The method described in British Pharmacopoeia (2016) was co-validated for specificity, linearity, precision and accuracy. VGB extemporaneous preparations were prepared in triplicate and placed in amber glass and PET bottles, which were stored under three different conditions: at room temperature (15 to 30 °C), under refrigeration (2 to 8 °C), and oven (40 °C). Samples of preparations stored at room temperature and refrigeration were collected every 7 days along 35 days. The same was done for solutions kept at 40 °C, but for a period of 28 days. It was also analyzed the preparations pH for each sampling time VGB extemporaneous preparations were analyzed by HPLC and demonstrated variations within the limits of British Pharmacopoeia (2016) up to 21 days in amber glass and PET bottles at room and refrigerated temperatures. VGB content for preparations kept in oven decreased above 10% after 7 days of study. The lowest pH change occurred in amber glass bottle stored under refrigeration. Results of this study can be applied as a reference for VGB extemporaneous preparation in hospital, once it was demonstrated the reliability of storage time interval and proper conditions for the use. Thus, pediatric patients with fractionated doses or patients using nasogastric probe will have adequately prepared extemporaneous preparations, reducing the risk of dilution errors and microbiological contamination.