The risk-adjusted Bernoulli cumulative sum (CUSUM) chart developed by Steiner et al. (2000) is an increasingly popular tool for monitoring clinical and surgical performance. In practice, however, use of a fixed control limit for the chart leads to quite variable in-control average run length (ARL) performance for patient populations with different risk score distributions. To overcome this problem, the simulation-based dynamic probability control limits (DPCLs) patient-by-patient for the risk-adjusted Bernoulli CUSUM charts is determined in this study. By maintaining the probability of a false alarm at a constant level conditional on no false alarm for previous observations, the risk-adjusted CUSUM charts with DPCLs have consistent in-control performance at the desired level with approximately geometrically distributed run lengths. Simulation results demonstrate that the proposed method does not rely on any information or assumptions about the patients' risk distributions. The use of DPCLs for risk-adjusted Bernoulli CUSUM charts allows each chart to be designed for the corresponding particular sequence of patients for a surgeon or hospital. The effect of estimation error on performance of risk-adjusted Bernoulli CUSUM chart with DPCLs is also examined. Our simulation results show that the in-control performance of risk-adjusted Bernoulli CUSUM chart with DPCLs is affected by the estimation error. The most influential factors are the specified desired in-control average run length, the Phase I sample size and the overall adverse event rate. However, the effect of estimation error is uniformly smaller for the risk-adjusted Bernoulli CUSUM chart with DPCLs than for the corresponding chart with a constant control limit under various realistic scenarios. In addition, there is a substantial reduction in the standard deviation of the in-control run length when DPCLs are used. Therefore, use of DPCLs has yet another advantage when designing a risk-adjusted Bernoulli CUSUM chart. These researches are results of joint work with Dr. William H. Woodall (Department of Statistics, Virginia Tech). Moreover, DPCLs are adapted to design the risk-adjusted CUSUM charts for multiresponses developed by Tang et al. (2015). It is shown that the in-control performance of the charts with DPCLs can be controlled for different patient populations because these limits are determined for each specific sequence of patients. Thus, the risk-adjusted CUSUM chart for multiresponses with DPCLs is more practical and should be applied to effectively monitor surgical performance by hospitals and healthcare practitioners. This research is a result of joint work with Dr. William H. Woodall (Department of Statistics, Virginia Tech) and Mr. Justin Loda (Department of Statistics, Virginia Tech). / Ph. D.

A epilepsia do lobo temporal (ELT), além de ser o tipo de epilepsia focal mais comum, também é a que tem maior refratariedade à farmacoterapia, correspondendo à 30% dos casos. Se não tratada pode levar à piora da qualidade de vida, déficits cognitivos e risco de morte (ENGEL, 1998). O tratamento padrão para ELT farmacorresistente é a remoção cirúrgica das estruturas envolvidas (ENGEL, 1996), com taxas de cura que podem chegar a 80% (ENGEL, 2001a). Os benefícios da cirurgia são: diminuição da frequência e severidade das crises, diminuição da mortalidade, melhores índices de qualidade de vida. Recomenda-se que pacientes com ELT farmacorresistentes sejam referenciados a um centro de cirurgia de epilepsia para avaliar a possibilidade de intervenção cirúrgica (ENGEL et al., 2003). Em nosso estudo, avaliamos 621 pacientes com epilepsia mesial do lobo temporal, com confirmação histopatológica de esclerose hipocampal, que realizaram ressecção do lobo temporal no Centro de Cirurgia de Epilepsia de Ribeirão Preto (CIREP) entre os anos de 1994 até 2011. Avaliamos os principais fatores preditores que influenciam no sucesso cirúrgico relacionados ao controle das crises epilépticas, através de um estudo longitudinal e retrospectivo. Realizamos o acompanhamento clínico desses pacientes por até 23 anos, com média de 11,6 anos (± 5,3) e encontramos que 73,6% dos pacientes ficaram livres de crises com alteração da consciência (Engel I) e 84,7% tiveram um bom prognóstico cirúrgico (Engel I + II). Esse prognóstico foi relativamente mantido ao longo do tempo em 65 % dos pacientes, após 20 a 23 anos da cirurgia. Encontramos que a história de crise febril foi um fator de bom prognóstico, enquanto que a aura dismnésica e olfatória foram fatores de mau prognóstico. Em relação ao tipo de técnica cirúrgica, a lobectomia temporal anteromesial (com ressecção do polo temporal), obteve significativo melhor prognóstico (78,6% Engel I) em relação à cirurgia que poupa o polo temporal (67,2% Engel I), p=0,002*, sugerindo que as conexões neurais envolvidas na zona epileptogênica podem estar além das estruturas mesiais. Concluímos que a cirurgia para epilepsia é um procedimento seguro, com baixos índices de complicações pós-operatórias e bons resultados em longo prazo. / Temporal lobe epilepsy (TLE) is the most common type of focal epilepsy and the one that has greater refractoriness to pharmacotherapy, corresponding to 30% of the cases. If untreated, it can lead to worsening of quality of life, cognitive deficits and risk of death (ENGEL, 1998). The standard treatment for medically refractory TLE is the surgical removal of the structures involved (ENGEL, 1996), with good outcomes rates that can reach to 80% (ENGEL, 2001a). The benefits of the surgery are: decrease in frequency and severity of seizures, decrease in mortality, better indexes of quality of life and higher rates of return to school and work. It is recommended that medically refractory TLE patients should be referred to an epilepsy surgery center to evaluate the possibility of surgical intervention (ENGEL et al., 2003). In our study, we evaluated 621 patients with mesial temporal lobe epilepsy secondary to hippocampal sclerosis (MTLE-HS), who underwent a temporal lobectomy at our epilepsy surgery center (CIREP) between the years 1994 to 2011. We evaluated the main predictive factors that influence the surgical outcome, through a longitudinal and retrospective study. We performed the clinical follow-up for up to 23 years and the mean follow-up was 11,6 years (± 5,3). We found that 73,6 % of the patients were free of disabling seizures and 84,7% had a good surgical outcome (Engel I + II). This prognosis was relatively maintained over the time in 65% of patients after 20 to 23 years of surgery. We found that history of febrile seizure was a good prognostic factor, whereas the dysmnesic and olfactory aura were factors of poor outcome. Regarding the type of surgical technique, the anteromesial temporal lobe resection obtained significant better outcomes (78,6% Engel I) in relation to the surgery who preserve the temporal pole (67,2% Engel I), p value = 0,002*, suggesting that the neuronal networks involved in the epileptogenic zone may be beyond mesial structures. We conclude that epilepsy surgery is a safe procedure, with low rates of postoperative complications and good long-term results.