Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 5 uppsatser.

Introdução: Em pacientes críticos, como os grandes queimados, todos os parâmetros farmacocinéticos (absorção, distribuição, metabolismo e excreção) de muitas classes de drogas, incluindo antimicrobianos, estão alterados. Devido à forte associação entre a terapia antimicrobiana adequada em pacientes com queimaduras e mortalidade, intervenções como o monitoramento terapêutico de drogas podem ser uteis para otimizar a concentração sérica desses agentes em diferentes estágios do estado hiperdinâmico. Portanto, é possível melhorar desfecho clínico e sobrevivência além de reduzir o desenvolvimento de resistência. O objetivo deste estudo foi analisar o impacto em mortalidade de uma estratégia de ajuste de dose de acordo com o monitoramento terapêutico e modelagem farmacocinética/farmacodinâmica em pacientes de uma Unidade de Terapia Intensiva (UTI) para Queimados. Métodos: Um estudo comparativo, retrospectivo, foi conduzido entre pacientes admitidos com pneumonia, infecção em queimadura, infecção de corrente sanguínea e/ou infecção do trato urinário associados à assistência à saúde em uma UTI para Queimados do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). Estes pacientes foram divididos em dois grupos: aqueles admitidos de maio de 2005 a outubro de 2008 que receberam antibioticoterapia em regime de dose convencional proposto pelo Grupo de Controle de Infecção Hospitalar do HC-FMUSP e aqueles admitidos de novembro de 2008 a junho de 2011 que receberam terapia antimicrobiana com dose ajustada de acordo com o monitoramento plasmático e modelagem farmacocinética. Características gerais dos dois grupos foram analisadas e desfechos clínicos (melhora dos sinais e sintomas da infecção), mortalidade em 14 dias e mortalidade hospitalar foram comparados. Resultados: 63 pacientes admitidos na UTI de Queimados apresentaram os critérios de inclusão para o grupo de tratamento convencional e 77 para o grupo de tratamento monitorado. Comparando dois grupos homogêneos em suas características gerais, houve diferenças quanto ao número de desbridamentos realizados e história de alcoolismo e uso de drogas ilícitas, mais frequentes no grupo de tratamento monitorado. Melhora clínica ocorreu em 56% dos pacientes sob regime monitorado e a mortalidade hospitalar foi similar entre os grupos. Pertencer a um dos grupos de tratamento não afetou o prognóstico. Na análise multivariada final, variáveis significativamente associadas com mortalidade hospitalar foram superfície corporal queimada maior que 30%, idade mais avançada e sexo masculino. Conclusão: Nosso estudo demonstrou que a estratégia de monitoramento terapêutico de antimicrobianos não alterou prognóstico de pacientes queimados. Acreditamos que são necessários mais estudos para embasar esta estratégia / Introduction: In critical patients, such as burn patients, pharmacokinetic parameters (absorption, distribution, metabolism and excretion) of many classes of drugs, including antibiotics, are altered. The aim of this study was to compare two groups of burned patients under treatment for healthcare associated infections with and without therapeutic drug monitoring (TDM) based on PK/PD modeling. Methods: A comparative study was conducted with patients with healthcare-associated pneumonia, burn infection, bloodstream infection and urinary tract infection in the Burn Intensive Care Unit (ICU) of a tertiary-care hospital. These patients were divided into two groups: 1) those admitted from May 2005 to October 2008 who received conventional antimicrobial dose regimen; and 2) those admitted from November 2008 to June, 2011 who received antibiotics with doses adjusted according to plasma monitoring and pharmacokinetics modeling. General characteristics of the groups were analyzed and clinical outcomes, 14-day and in-hospital mortality. Results: 63 patients formed the conventional treatment group and 77 the monitored treatment group. The groups were very homogeneous. Improvement occurred in 56% of the patients under monitored treatment and the in-hospital mortality was similar between groups. In the final multivariate models, variables significantly associated with in-hospital mortality were total burn surface area (TBSA) > 30%, older age and male sex. Treatment group did not affect the prognosis. Conclusions: TDM for antimicrobial treatment did not alter the prognosis of burn patients. More trials are needed to support the use of TDM to optimize treatment in burn patients

Magister Scientiae - MSc / Indinavir is a potent and well tolerated protease inhibitor drug used as a component of the highly active antiretroviral therapy (HAART) of HIV/AIDS, which results in pharmacokinetics that may be favourable or adverse. These drugs work by maintaining a plasma concentration that is sufficient to inhibit viral replication and thereby suppressing a patient’s viral load. A number of antiretroviral drugs, including indinavir, undergo metabolism that is catalysed by cytochrome P450-3A4 enzyme found in the human liver microsomes. The rate of drug metabolism influences a patient’s response to treatment as well as drug interactions that may lead to life-threatening toxic conditions, such as haemolytic anaemia, kidney failure and liver problems. Therapeutic drug monitoring (TDM) during HIV/AIDS treatment has been suggested to have a potential to reduce drug toxicity and optimise individual therapy. A fast and reliable detection technique, such as biosensing, is therefore necessary for the determination of a patient’s metabolic profile for indinavir and for appropriate dosing of the drugs. In this study biosensors developed for the determination of ARV drugs comprised of cysteamine self-assembled on a gold electrode, on which was attached 3-mercaptopropionic acid-capped palladium telluride (3-MPA-PdTe) or thioglycolic acid-capped palladium telluride (TGA-PdTe) quantum dots that are cross-linked to cytochrome P450-3A4 (CYP3A4) in the presence of 1-ethyl-3(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide. The quantum dots were synthesized in the presence of capping agents (3-MPA or TGA) to improve their stability, solubility and biocompatibility. The capping of PdTe quantum dots with TGA or 3-MPA was confirmed by FTIR, where the SH group absorption band disappeared from the spectra of 3-MPA-PdTe and TGA-PdTe. The particle size of the quantum dots (< 5 nm) was estimated from high resolution transmission electron microscopy (HRTEM) measurements. Optical properties of the materials were confirmed by UV-Vis spectrophotometry which produced absorption iii bands at ~320 nm that corresponded to energy band gap values of 3 eV (3.87 eV) for TGAPdTe (3-MPA-PdTe) quantum dots. The electrocatalytic properties of the quantum dots biosensor systems were studied by cyclic voltammetry (CV) for which the characteristic reduction peak at 0.75 V was used to detect the response of the biosensor to indinavir. Results for indinavir biosensor constructed with 3-MPA-SnSe quantum dots are also reported in this thesis. The three biosensors systems were very sensitive towards indinavir; and gave low limits of detection (LOD) values of 3.22, 4.3 and 6.2 ng/mL for 3-MPA-SnSe, 3-MPA-PdTe and TGA-PdTe quantum dots biosensors, respectively. The LOD values are within the ‘maximum plasma concentration’ (Cmax) value of indinavir (5 - 15 ng/mL) normally observed 8 h after drug intake.

O Micofenolato Mofetil (MMF) é amplamente utilizado em transplantes de órgãos sólidos e tem como seu metabólito ativo o ácido micofenólico (MPA). A alta variabilidade intra e interindividual dos níveis plasmáticos de MPA em pacientes transplantados renais que recebem a mesma dose de MMF, a combinação com diferentes imunossupressores que afetam seu metabolismo e a oscilação destes níveis com o tempo decorrido após o transplante justificam a sua monitorização. Pequenas mudanças na dose de MMF podem comprometer a eficácia terapêutica. O objetivo deste trabalho foi avaliar a farmacocinética de duas formulações de MMF. Estudouse um ensaio para a dosagem de ácido micofenólico (MPA) plasmático (EMIT® 2000, Dade Behring) e a seguir, a biodisponibilidade da nova formulação de MMF disponibilizada por Strides Arcolab (MMF-SA), comparativamente ao CellCept® em pacientes transplantados renais estáveis. A metodologia de imunoensaio enzimático (EMIT) apresenta resultados relativamente mais elevados em relação à cromatografia líquida de alta resolução, devido à reação cruzada do metabólito acil glucoronídeo de MPA (AcMPAG) com o anticorpo presente no reagente. O método é capaz de detectar não só o MPA, mas também o seu metabólito ativo AcMPAG, o que pode representar uma vantagem. Comparamos o método EMIT com cromatografia líquida de alta resolução acoplada à espectrometria de massas (LC-MS/MS) e obtivemos r2 = 0,9612. O método apresentou: sensibilidade analítica de 0,02 ± 0,0016ug/mL; limite de detecção de 0,01 ± 0,0015ug/mL; linearidade de 14,58 ± 0,3300ug/mL; coeficientes de variação, intraensaio de 2,14% - 5,09% e interensaio de 4,18% - 5,02%. A estabilidade da amostra foi de 90 dias em temperatura de -20°C. Concluiu-se que a metodologia EMIT para dosagem de MPA é de fácil execução e apresenta boa precisão analítica. Participaram do estudo de biodisponibilidade, vinte e quatro pacientes adultos, transplantados renais, que já recebiam o CellCept® em combinação com Tacrolimus (n = 14), ciclosporina (n= 7) ou sem inibidores de calcineurina (n=3). Todos recebiam prednisona. As duas drogas foram administradas em esquema cruzado, com intervalo de uma semana entre as farmacocinéticas. Neste intervalo, os pacientes continuaram recebendo CellCept®. Foram analisadas as curvas farmacocinéticas de 12 horas para cada uma das duas formulações, nas mesmas doses equimolares. As médias ± SE das medidas de concentração máxima (Cmax) e da área sob a curva (AUC), para CellCept®, não foram estatisticamente diferentes das médias ± SE para MMF-SA (11,29 ± 1,35ug/mL versus 11,05 ± 1,08ug/mL e 49,11 ± 5,15ug.h/mL versus 47,59 ± 3,99 ug.h/mL), respectivamente. Da mesma forma, o intervalo de confiança 90% de MMF-SA / CellCept® para Cmax (93,57% - 121,73%) e para AUC 0-12h (93,75% - 108,90%) ficaram dentro do intervalo de bioequivalência (80% - 125%). Concluímos que CellCept® pode ser substituído com segurança pela formulação MMF-SA genérica em pacientes transplantados renais estáveis. / Mycophenolate mofetil (MMF) is largely used in solid organ transplantation. Mycophenolic Acid (MPA) is the active metabolite of MMF. The high intra and interpatients variability of the MPA plasma levels in transplant recipients under the same dose of MMF, the association with immunosuppressant drugs that change the MPA metabolism and pharmacokinetic parameters over time may cause impact in the optimal dose of MMF. The therapeutic monitoring of MPA may improve the efficacy and safety. The aim of this study was to: 1 -to validate the EMIT assay for MPA monitoring and 2: to assess the bioavailability of two MMF formulations. The performance of the EMIT® 2000 Dade Behring Mycophenolic acid enzimatic immunoassay was evaluated. There was a high correlation between the LC-MS/MS and EMIT (r2 = 0.9612). Because of the cross-reactivity of the antibody used in the EMIT assay with the active acyl glucuronide metabolite (AcMPAG), the EMIT concentrations are higher than those from high performance liquid chromatography (HPLC).The analytic sensitivity was 0.02 ± 0.0016ug/mL; detection limit 0.01 ± 0.0015ug/mL; linearity 14.58 ± 0.3300ug/mL. The CV of within-day precision was 2.14% - 5.09% and the CV of between-days precision was 4.18% - 5.02%. The sample stability was 90 days at - 20°C. The EMIT assay is easily performed and fulfills all the requirements for an assay. We studied the MMF formulation from Strides Arcolab (MMF-SA) and CellCept® in twenty-four adult, renal transplanted patients, receiving MMF (CellCept®), before the bioavailability study, combined with tacrolimus (n = 14), cyclosporine (n = 7) or without CNI (n = 3). All patients received prednisone. They had a 12 hours pharmacokinetics (PK) of total MPA measured after the same equimolar doses for the two formulations. The PK analysis revealed two mean PK curves that overlaid over each other. Mean ± SE of maximum concentration (Cmax) and area under the time-concentration curve (AUC) of CellCept® were not statistically different from the generic MMF-SA (11.29 ± 1.35 ug/mL vs 11.05 ± 1.05 ug/mL and 49.11 ± 5.15 ug.h/mL vs 47.59 ± 3.99 ug.h/mL, respectively). In the same way the MMF-SA/CellCept® 90% confidence interval for both: Cmax (93.57% -121.73%) and AUC0-12h (93.75% - 108.90%) was within the bioequivalence interval (80%-125%). In renal transplanted patients, CellCept® can be switched by the generic MMF formulation.

O monitoramento terapêutico da concentração de vancomicina é uma forma de melhorar a segurança e a eficiência no tratamento com este antibiótico. A cromatografia líquida de alta eficiência (CLAE) é considerada padrão ouro para a quantificação desta droga. No entanto a análise exige que sejam realizados vários procedimentos de purificação e análise da amostra, o que reduz sua aplicabilidade ao uso clínico. Atualmente, não há consenso quanto aos níveis séricos adequados ao tratamento do neonato ou de como as doses devem ser ajustadas. Este trabalho propõe um protocolo de monitorização terapêutica da vancomicina e desenvolve e valida um método simplificado, de baixo custo e menor volume de amostra necessário para quantificação da concentração sérica da vancomicina através de CLAE com detecção por arranjo de diodos. As amostras foram extraídas por precipitação de proteínas com ácido trifluoroacético (ATF), o sobrenadante foi injetado diretamente no sistema cromatográfico. A fase móvel consistiu de ATF à concentração de 0,014% (pH 2.800) em água ultrapura e acetonitrila (92:8, v/v), sob fluxo de 2 mL/min por eluição em método isocrático e temperatura de 40 oC. As respostas foram monitoradas no comprimento de onda de 230,9 nm. A validação foi conduzida de acordo com a resolução da RDC n.o 27, de 17 de maio de 2012 da ANVISA. O analito e o padrão interno (7-hidroxicumarina) foram eluídos em torno de 5.1 min e 10.3 min respectivamente. A linearidade do método foi determinada entre 2 e 70 mg/L com correlação linear de superior a 0.999. O método mostrou-se adequado a aplicação proposta, com vantagens volume de amostra exigido, o processo de extração simplificado e resultados satisfatórios com relação às precisão, exatidão, estabilidade e seletividade. O método de análise testado em 17 amostras reais de 10 pacientes com resultados satisfatórios. O protocolo de monitorização terapêutica foi adequadamente desenvolvido. / Therapeutic monitoring of vancomycin concentration can improve the safety and efficiency of the treatment with this antibiotic. High-performance liquid chromatography (HPLC) is considered gold standard for quantification for this drug. However the analysis requires multiple procedures for purification and analysis of the sample, which reduces their applicability for clinical use. There`s currently no consensus on vancomycin serum target levels and dose adjustment among newborns. This paper proposes a vancomycin therapeutic monitoring protocol and develops and validates a low cost, simplified method, with smaller sample volume requirement for serum concentration of vancomycin determination by using HPLC with diode array. Samples were extracted by protein precipitation with trifluoroacetic acid (TFA), supernatant was injected directly into the chromatographic system. Mobile phase consisted of TFA 0.014% (pH 2.800) in ultrapure water and acetonitrile (92:8, v /v) under flow rate of 2 mL / min eluting in isocratic method in 40oC. Response were monitored at a wavelength of 230.9 nm. Validation was conducted in accordance with the resolution of the RDC No. 27 of May 17, 2012 ANVISA. Vancomycin and internal standard (7-hydroxycoumarin) were eluted at approximately 5.1 min. and 10.3 min respectively. Linearity was assessed between 2 and 70 mg /L with linear correlation greater than 0.999. The method proved to be suitable for the proposed application, with the advantages of less sample volume required, simplified extraction and achieved satisfactory results of precision, accuracy, stability and selectivity. This method was tested in 17 real samples from 10 patients with satisfactory results. The drug monitoring protocol was successfully developed.

Introdução: Eventos adversos a medicamentos (EAM) representam um importante problema de saúde pública, sendo associados à morbimortalidade, maior taxa de permanência hospitalar e elevação de custos. Os idosos e os pacientes de unidade de terapia intensiva (UTI) são grupos de risco para a ocorrência desses eventos. O uso de rastreadores, que representam situações indicativas de potenciais EAM, simplifica a detecção de EAM por meio do screening sistemático de prontuários, possibilitando a mensuração da taxa dessas adversidades continuamente e permitindo avançar na prática de segurança do paciente crítico. Objetivo: Analisar os eventos adversos a medicamentos e fatores associados em pacientes idosos de UTI. Método: Coorte retrospectiva conduzida com idosos internados em UTI do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. A amostra consecutiva foi composta por prontuários de idosos, hospitalizados por no mínimo 24 horas para tratamento clínico ou cirúrgico e que tenham recebido pelo menos um medicamento. Os pacientes foram acompanhados da internação até a saída da UTI por alta ou óbito. Para a identificação dos EAM utilizou-se o instrumento do Institute for Healthcare Improvement (IHI) adaptado para a realidade local, que inclui rastreadores medicamentosos, bioquímicos e clínicos. Foram coletadas variáveis demográfico-clínicas, relativas ao regime terapêutico, exames laboratoriais, intervenções durante a internação e sinais/sintomas clínicos. A variável dependente foi a ocorrência de EAM. Os dados foram analisados por meio dos testes Qui-quadrado, Exato de Fisher, Correlação de Pearson e regressão logística multivariada, com significância de p0,05. Resultados: A incidência de pacientes com EAM foi 22,3% e o número de EAM por 100 pacientes foi 32,3, média de 1,4 EAM. A amostra foi composta predominantemente por homens (54,6%), idosos jovens (68,8%), internados para procedimentos clínicos (67,4%) e sujeitos a polifarmácia (70,6%). Sangramento (21,7%), injúria renal aguda (20%), hipotensão (18,3%), náusea/vômito (15%) e hipoglicemia (13,3%) foram os EAM mais frequentes. Identificou-se correlação positiva entre EAM e as variáveis comorbidades (r=0,189), tempo de internação (r=0,288) e número de medicamentos prescritos (r=0,282). Os fatores de risco para EAM em UTI foram ventilação mecânica (OR= 2,614; IC95% 1,393 4,906; p= 0,003), injúria renal aguda (OR= 3,794; IC95% 1,688 8,527; p=0,001) e diabetes mellitus (OR= 3,280; IC 95% 1,703 6,315; p= 0,000). Conclusão: A ocorrência dos EAM mostrou-se correlacionada positivamente com atributos que são muito característicos de idosos admitidos em UTI, aspecto que pode servir de alerta aos profissionais que realizam o monitoramento desses eventos. / Introduction: Adverse drug events (ADE) represent an important public health problem, being associated with morbidity and mortality, a higher hospital stay rate and higher costs. The elderly and intensive care patients (ICU) are at risk groups for the occurrence of these events. The use of trackers, which represent situations indicative of potential ADE, simplifies the detection of ADE through the systematic screening of medical records, making it possible to measure the rate of these adversities continuously and to advance in the practice of critical patient safety. Objective: To analyze adverse drug events and associated factors in elderly ICU patients. Method: Retrospective cohort conducted with elderly patients admitted to ICU at Hospital das Clínicas, Medical School, University of São Paulo. The consecutive sample consisted of records of the elderly, hospitalized for at least 24 hours for clinical or surgical treatment and who received at least one medication. Patients were followed up for ICU discharge or discharge. The Institute for Healthcare Improvement (IHI) instrument adapted to the local reality, which includes drug, biochemical and clinical trackers, was used to identify the ADE. Demographic and clinical variables related to the therapeutic regimen and laboratory tests, therapeutic interventions during hospitalization, clinical signs and symptoms were collected. The dependent variable was the occurrence of ADE. Data were analyzed using the Chi-square test, Fisher\'s exact test, Pearson\'s correlation and multivariate logistic regression, with significance of p0.05. Results: The incidence of ADE patients was 22.3% and the number of ADE per 100 patients was 32.3, a mean of 1.4 ADE. Men (54.6%), young adults (68.8%), hospitalized for clinical procedures (67.4%) and polypharmacy (70.6%). Bleeding (21.7%), acute renal injury (20%), hypotension (18.3%), nausea / vomiting (15%) and hypoglycaemia (13.3%) were the most frequent events. A positive correlation between EAM and comorbidities (r = 0.189), length of hospital stay (r = 0.288), and number of drugs prescribed (r=0.282) were identified. The risk factors for EAM in the ICU were mechanical ventilation (OR= 2,614; IC95%, 1,393 4,906; p= 0,003), acute renal injury (OR= 3,794; IC95% 1,688 8,527; p=0,001) and diabetes mellitus (OR= 3,280; IC 95% 1,703 6, 315; p= 0,000). Conclusion: The occurrence of ADE was positively correlated with attributes that are very characteristic of the elderly admitted to the ICU, an aspect that can serve as an alert to the professionals who perform the monitoring of these events.

Para avaliar a exposição ao ácido micofenólico (MPA) na fase inicial pós-transplante renal, receptores foram destinados para receber tacrolimo (n=33) ou ciclosporina (n=19, controle) com MMF. Foram feitas coletas de farmacocinética (AUC) do inibidor de calcineurina e MPA nos dias 7, 14, 30, 60 e 180 pós-transplante. Dos dias 14-180, a MPA-AUC foi mais elevada no grupo tacrolimo devido a um maior segundo pico de MPA. Com doses fixas de MMF, uma grande porcentagem de curvas ficou abaixo da faixa terapêutica. No dia 7, a equação que emprega a concentração pré-dose (C0) e na segunda hora (C2) foi a mais precisa para estimar AUC. Após o dia 7, a equação que utiliza C2 foi a mais precisa. A exposição ao MPA nos primeiros seis meses após transplante renal é maior sob tacrolimo do que ciclosporina. Entretanto, para qualquer inibidor de calcineurina empregado com MMF, uma equação que emprega C0 e C2 (dia 7) e C2 isoladamente (após o dia 7), permite a monitoração de MPA com grande precisão / To evaluate the exposure to mycophenolic acid (MPA) early after renal transplantation, recipients were allocated to tacrolimus (n = 33) or Neoral (n =19, control) plus MMF. Pharmacokinetic curves (AUC) of calcineurin inhibitor and MPA were drawn on days 7, 14, 30, 60 and 180 post-transplant. From days 14-180, MPA-AUC was higher in tacrolimus group due to a higher second MPA peak. With fixed MMF doses, a great amount of curves fell below the proposed therapeutic range. On day 7, the equation that uses pre-dose (C0) and second-hour (C2) concentrations was the most accurate. After day 7, the equation that uses C2 alone was the most accurate. Exposure to MPA during the first six months after transplantation is higher under tacrolimus than Neoral. Nevertheless, despite the calcineurin inhibitor associated with MMF, an equation that uses C0 and C2 up to day 7 and C2 thereafter allows precise MPA monitoring

E-hälsa blir allt mer relevant i och med att IT utvecklas i samhället, och kan hjälpa sjukvården att bli effektivare. Det finns stora svårigheter för läkare att få en samlad hälsobild över patientens läkemedelsanvändning, vilket gör att läkaren har svårt att fatta beslut rörande patientens medicinering. Dessa problem grundar sig i den bristfälliga informationsöverföringen mellan vårdinstanser. Ehälsomyndigheten har tagit sig ann denna utmaning genom att skapa en plattform som ska göra det enklare för patienten att hantera all sin hälsoinformation. Till denna plattform kan utvecklare utveckla mobilapplikationer med fokus på hälsa. Vilket kan skapa nya utmaningar då de ska anpassas för att alla ska kunna använda dem. En grupp som vanligen kan känna sig utanför är seniorer och speciellt de över 75 år. Seniorer kan inte alltid använda sig av de applikationer som finns tillgängliga i samma utsträckning, då de oftast är utformade efter en mer generell användare. Studien har undersökt vilka brister det finns i de generella designprinciperna och riktlinjer riktade till seniorer och hur dessa behöver anpassas för att få ett mer användbart gränssnitt. Studien utformade en prototyp utifrån etablerade designprinciper som adresserar problemet med läkemedelsuppföljning och utförde sedan användbarhetstester av denna prototyp. Seniorer fick interagera med prototypen under observationer, där fokuset låg i att finna vilka svårigheter som kan finnas med gränssnittet. Svårigheterna respondenterna upplevde analyserades och genererade rekommendationer på förändringar som till viss del implementerades i prototypen innan studien utförde sitt andra användbarhetstest. Resultatet visar att de etablerade designprinciperna till stor del kan följas vid utformandet av gränssnitt för seniorer men det finns behov av att prioritera vissa principer framför andra samt att dra vissa principer till sin spets vilket redogörs för i slutet av denna studie. / E-health is becoming more and more relevant in society since IT is growing, which can help the health care to be more effective. Doctors have big problems to get a collected health view of the patient’s drug usage, which makes it hard for doctors to prescribe new drugs to the patient. These problems are based on the lack of information transfer between health care agencies. The department of E-health (Ehälsomyndigheten) are creating a platform to take on this problem. This platform will make it easier for patients to handle their health information. System developers can develop mobile applications, focused on health, to this platform. Applications need to be customized so that everyone can use them, but are usually designed for the general user. Seniors, especially those over 75 years of age, can’t always make use of the applications to the same extent which can make them feel left out. This study has investigated what flaws there are to the general design principles and guidelines for the senior citizens. And how the design principles should be customized to make a more useful interface. The study developed a prototype from established design principles that addresses the problem with drug monitoring. The prototype was tested in usability tests where seniors interacted with the application during observations. The focus was to find what difficulties the seniors had interacting with the interface. The findings of the test were analyzed and generated recommendations on changes that were partially implemented in the prototype before the study conducted its second usability test. The results show that the established design principles can be followed for the most part, in the design of interfaces for seniors, but there is a need to prioritize certain principles over others. The results also indicate that some design principles need to be intensified for the senior citizens to find the interface useful. The thesis is written in Swedish.Keywords:

>Magister Scientiae - MSc / The aim of this study was to compare the trough plasma levels of Aspen-Vancomycin® (AV); and Sandoz-Vancocin CP® (SV) in premature infants with suspected Methicillin Resistant Staphylococcus aureus (MRSA) infection. The study was designed as a prospective, double blind, randomised trial involving male and female premature infants admitted in the Neonatal Intensive care Unit (NICU) at Netcare Blaauwberg and N1-city Hospitals for treatment of suspected MRSA-infection between April 2012 and June 2013. The inclusion criteria were: 29-35 weeks postmenstrual age (PMA), informed and written consent from parents of each premature infant enrolled in the study. Blood samples (0.3-0.4ml) were collected for renal function test and vancomycin trough levels determination. Blood samples for vancomycin trough level assay were collected thirty minutes prior to the administration of the third dose of vancomycin. Statistical analysis was performed and estimation was made giving an indication of how many infants will be needed to make the study statistically significant. Wilcoxon Two-Sample test was performed to determine the p-values and Spearman correlation coefficients were used to determine the correlation between trough levels and variables. P-values < 0.05 were considered significant. A total of 19 premature infants met with study criteria, 10 (5 females and 5 males) received AV and 9 (6 females and 3 males) receive d SV. There was no statistical significant difference between the demographic (GA, BW, PMA, PNA, weight at trial entry, height at trial entry) and biological (albumin, serum creatinine concentration and glomerular filtration rate) parameters of the premature infants in the AV and SV group. There were no statistical significant difference between trough level 1 of AV and SV, although trough level 1 had a lower trend in the SV group (p=0.118). No AV trough level 1 was below the minimum effective concentration (<5μg/ml). It was found that 30% of AV trough level 1 was within the therapeutic range (5-10μg/ml) and 70% of AV trough level 1, were above minimum toxic concentration (>10mg/l). It was found that 22.2% of SV trough level 1 was below minimum effective concentration, 44.4% of SV trough level 1 was within therapeutic range and 33.3% of trough level 1 was above minimum toxic concentration. No correlation was found between trough level 1 and the demographic and biological parameters of the premature infants in the AV group. SV had a positive correlation with GA, BBW, PMA and a negative correlation with PNA

Since the Institute of Medicine highlighted the devastating impact of medical errors in their seminal report, “To Err is Human” (2000), efforts have been underway to improve patient safety. A portion of medical errors are due to medication errors, and a large portion of these can be attributed to inadequate laboratory monitoring. In this thesis, I attempt to address this small but important corner of this patient safety endeavor. Why are patients not getting their laboratory monitoring tests? Do they fail to complete them or do doctors not order the tests in the first place? Which prescribers and which patients are least likely to do what is needed for testing to happen and what interventions would be most promising? To address these questions, I conducted a systematic review of existing interventions. I then proceeded with three aims: 1) To identify reasons that patients give for missing monitoring tests; 2) To identify patient and provider factors associated with monitoring test ordering; and 3) To identify patient and provider factors associated with completion of ordered testing. To achieve these aims, I worked with patients and data at the Fallon Clinic. For aim 1, I conducted a qualitative analysis of their reasons for missing tests as well as reporting completion and ordering rates. For aims 2 and 3, I used electronic medical record data and conducted a regression with patient and provider characteristics as covariates to identify factors contributing to test ordering and completion. Interviews revealed that patients had few barriers to completion, with forgetting being the most common reason for missing a test. The quantitative studies showed that: older patients with more interactions with the health care system were more likely to have tests ordered and were more likely to complete them; providers who more frequently prescribe a drug were more likely to order testing for it; and drug-test combinations that were particularly dangerous, indicated by a black box warning, were more likely to have appropriate ordering, though for these combinations, primary care providers were less likely to order tests appropriately, and patients were less likely to complete tests. Taken together, my work can inform future interventions in laboratory monitoring and patient safety.