A following study on vancomycin demonstrated the differing pharmacokinetics during the course of a septic insult, day 2 pharmacokinetics differing from day 7. / An important study showed that some septic patients with "normal" serum creatinines can have very high creatinine clearances. It follows that drugs which are renally excreted will have high clearances and illustrates why many of the above patients had low serum levels of antibiotic, a reason why some ICU patients require different dosing to ward patients. / Due to the required fluid loading and inotropic use in septic patients, creatinine clearances and drug clearances are often raised. This results in low serum concentrations at the end of a standard dosing interval. / My beta-lactam antibiotic work has repeatedly demonstrated low serum levels at the end of the standard dosing interval. In view of beta-lactam time-dependent kill characteristics we designed a continuous infusion protocol which we validated in a follow-up paper. / The inflammatory response of infections involves endothelial damage and capillary permeability. With associated fluid shifts of severe sepsis and treatment thereof, the volume of distribution (Vd) of antibiotics that distribute into the extracellular space (aminoglycosides, glycopeptides) is high. Peak serum levels for these antibiotics are therefore lower than those found in non-critically ill and in normal volunteers. It is noteworthy that this change in Vd is not apparent with drugs that have good tissue penetration (e.g. ciprofloxacin). / This thesis is a compilation of 11 of my prospectively designed studies plus extracts from 5 published reviews, focusing on pharmacokinetic (PK) aspects of antibiotics in ICU patients, all published in internationally peer-reviewed journals. / Two large PK studies on ciprofloxacin (a drug that has excellent tissue penetration) designed to address possible PK differences over time, could not demonstrate this difference in adults nor in two groups of paediatric patients where differences in body water are significant. / Two papers investigated the pharmacokinetics of amicakin in adult and paediatric patients documenting the benefit of extended interval dosing. / We automatically assume that antibiotic prescribing data, collated from healthy volunteers and not so ill patients, can be transcribed into the Intensive Care Unit. This is not so. / Jeffrey Lipman. / "April 2005." / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1548. / Thesis (M.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 235-254). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.

Introdução: Diversos estudos têm demonstrado que os cuidados paliativos (CP) melhoram o controle dos sintomas, a satisfação e o suporte psicológico dos pacientes com câncer e de seus familiares. Há evidências de que quanto mais precoce for o ingresso do paciente em CP menor será a utilização de tratamentos agressivos no último mês de vida. Além disso, a potencial redução nos custos do tratamento na fase final da vida associado a CP também tem sido relatada na literatura. No Brasil, não há estudo que estime o uso de recursos e os custos dos cuidados paliativos para pacientes com câncer. Objetivos: Estimar os custos diretos médicos de cuidados paliativos para pacientes com câncer na perspectiva do Instituto do Câncer do Estado de São Paulo (ICESP). Métodos: Estudo de descrição de custo retrospectivo para estimar a utilização de recursos e os custos diretos médicos associados ao serviço de cuidados paliativos, sob a perspectiva do serviço de saúde (ICESP). A amostra incluiu pacientes maiores de 18 anos com câncer, que foram a óbito de 2010 a 2013 e que receberam pelo menos dois atendimentos em cuidados paliativos e/ou fizeram uso do hospice. Os prontuários eletrônicos e as bases de dados administrativas do Instituto foram as fontes de dados. Utilizou-se das metodologias de microcusteio e macrocusteio para estimar os custos unitários. Realizou-se ainda análises de sensibilidade univariada e multivariada. Os fatores que impactam os custos foram identificados por meio de modelos lineares generalizados. A associação entre cuidados paliativos precoces e indicadores de tratamento agressivo foi avaliada pelo teste qui-quadrado de Pearson e pelo teste exato de Fisher. Resultados: Entre os 2.985 pacientes que fizeram parte do estudo, o intervalo de tempo entre o início em cuidados paliativos e o óbito apresentou mediana de 34 dias. Os pacientes que ingressaram até três meses antes do óbito realizaram menos visitas à emergência (p < 0,001). O custo total foi de R$ 67.372.455,91, com custo médio por paciente de R$ 22.570,34. Os pacientes com câncer de cérebro foram os que apresentaram maior custo (R$ 35.488,47). Não houve diferença no custo do último mês de vida entre os pacientes que ingressaram mais precocemente e os que ingressaram mais tardiamente em cuidados paliativos. Os fatores preditores do custo foram idade do paciente, localização do câncer, local do óbito, número de internações, número de visitas à emergência, dias em hospice e dias em cuidados paliativos. Conclusão: Este estudo permitiu conhecer as práticas de um serviço de cuidados paliativos, apresentou a utilização de recursos e os custos nas diversas localizações do câncer sob a perspectiva do provedor e poderá contribuir para a discussão sobre o cuidado paliativo no Brasil / Introduction: Several studies have shown that palliative care (PC) improves symptoms control, treatment satisfaction and psychological support of patients with cancer and their families. There are evidences that demonstrate that the sooner a patient enters into PC, the lower the need for aggressive treatment in the last month of life. In addition, a potential reduction in treatment costs at the end of life is associated with PC. In Brazil, there is no study to date that reports on the use of resources and the cost of palliative care for cancer patients. Objectives: To estimate the direct medical costs of PC for cancer patients from perspective of Cancer Institute of the State of São Paulo (ICESP). Methods: Retrospective cost description study to estimate the use of resources and direct medical costs associated with PC service from the perspective of ICESP. Eligible patients were older than 18 years of age, received at least 2 consultations in PC and/or made use of a hospice and died between 2010 and 2013. Data were collected from electronic medical records and administrative databases of ICESP. Unit costs were estimated using micro-costing and macro-costing methodologies. Univariate and multivariate sensitivity analyses were performed. The predictors of costs were identified through generalized linear models. The association between early palliative care and aggressive treatment indicators was assessed using Pearson\'s chi-square test and Fisher\'s exact test. Results: Among the 2985 patients in the study, the median time from entry into PC until death was 34 days. Patients who entered earlier into PC ( >- 3 months before death) had fewer emergency visits (p < 0.001). Total cost was R$67.372.455,91 with an average cost per patient of R$22.570,34. Patients with brain cancer presented the highest cost (R$35.488,47). There was no difference in cost in the last month of life between patients who entered earlier and those who entered later into PC. The predictor factors of cost were patient\'s age, cancer site, place of death, number of hospitalizations, number of emergency visits, number of days in hospice and number of days in PC. Conclusion: This study allowed to know the practices of a palliative care service, presented the use of resources and costs in the different locations of cancer from the perspective of the provider and can contribute to discussion about palliative care in Brazil

Introdução: Diversos estudos têm demonstrado que os cuidados paliativos (CP) melhoram o controle dos sintomas, a satisfação e o suporte psicológico dos pacientes com câncer e de seus familiares. Há evidências de que quanto mais precoce for o ingresso do paciente em CP menor será a utilização de tratamentos agressivos no último mês de vida. Além disso, a potencial redução nos custos do tratamento na fase final da vida associado a CP também tem sido relatada na literatura. No Brasil, não há estudo que estime o uso de recursos e os custos dos cuidados paliativos para pacientes com câncer. Objetivos: Estimar os custos diretos médicos de cuidados paliativos para pacientes com câncer na perspectiva do Instituto do Câncer do Estado de São Paulo (ICESP). Métodos: Estudo de descrição de custo retrospectivo para estimar a utilização de recursos e os custos diretos médicos associados ao serviço de cuidados paliativos, sob a perspectiva do serviço de saúde (ICESP). A amostra incluiu pacientes maiores de 18 anos com câncer, que foram a óbito de 2010 a 2013 e que receberam pelo menos dois atendimentos em cuidados paliativos e/ou fizeram uso do hospice. Os prontuários eletrônicos e as bases de dados administrativas do Instituto foram as fontes de dados. Utilizou-se das metodologias de microcusteio e macrocusteio para estimar os custos unitários. Realizou-se ainda análises de sensibilidade univariada e multivariada. Os fatores que impactam os custos foram identificados por meio de modelos lineares generalizados. A associação entre cuidados paliativos precoces e indicadores de tratamento agressivo foi avaliada pelo teste qui-quadrado de Pearson e pelo teste exato de Fisher. Resultados: Entre os 2.985 pacientes que fizeram parte do estudo, o intervalo de tempo entre o início em cuidados paliativos e o óbito apresentou mediana de 34 dias. Os pacientes que ingressaram até três meses antes do óbito realizaram menos visitas à emergência (p < 0,001). O custo total foi de R$ 67.372.455,91, com custo médio por paciente de R$ 22.570,34. Os pacientes com câncer de cérebro foram os que apresentaram maior custo (R$ 35.488,47). Não houve diferença no custo do último mês de vida entre os pacientes que ingressaram mais precocemente e os que ingressaram mais tardiamente em cuidados paliativos. Os fatores preditores do custo foram idade do paciente, localização do câncer, local do óbito, número de internações, número de visitas à emergência, dias em hospice e dias em cuidados paliativos. Conclusão: Este estudo permitiu conhecer as práticas de um serviço de cuidados paliativos, apresentou a utilização de recursos e os custos nas diversas localizações do câncer sob a perspectiva do provedor e poderá contribuir para a discussão sobre o cuidado paliativo no Brasil / Introduction: Several studies have shown that palliative care (PC) improves symptoms control, treatment satisfaction and psychological support of patients with cancer and their families. There are evidences that demonstrate that the sooner a patient enters into PC, the lower the need for aggressive treatment in the last month of life. In addition, a potential reduction in treatment costs at the end of life is associated with PC. In Brazil, there is no study to date that reports on the use of resources and the cost of palliative care for cancer patients. Objectives: To estimate the direct medical costs of PC for cancer patients from perspective of Cancer Institute of the State of São Paulo (ICESP). Methods: Retrospective cost description study to estimate the use of resources and direct medical costs associated with PC service from the perspective of ICESP. Eligible patients were older than 18 years of age, received at least 2 consultations in PC and/or made use of a hospice and died between 2010 and 2013. Data were collected from electronic medical records and administrative databases of ICESP. Unit costs were estimated using micro-costing and macro-costing methodologies. Univariate and multivariate sensitivity analyses were performed. The predictors of costs were identified through generalized linear models. The association between early palliative care and aggressive treatment indicators was assessed using Pearson\'s chi-square test and Fisher\'s exact test. Results: Among the 2985 patients in the study, the median time from entry into PC until death was 34 days. Patients who entered earlier into PC ( >- 3 months before death) had fewer emergency visits (p < 0.001). Total cost was R$67.372.455,91 with an average cost per patient of R$22.570,34. Patients with brain cancer presented the highest cost (R$35.488,47). There was no difference in cost in the last month of life between patients who entered earlier and those who entered later into PC. The predictor factors of cost were patient\'s age, cancer site, place of death, number of hospitalizations, number of emergency visits, number of days in hospice and number of days in PC. Conclusion: This study allowed to know the practices of a palliative care service, presented the use of resources and costs in the different locations of cancer from the perspective of the provider and can contribute to discussion about palliative care in Brazil