Nas últimas décadas, houve aumento progressivo das infecções hospitalares por leveduras principalmente, do gênero Candida. A fonte de infecção pode ser endógena ou exógena, desde que esporos unicelulares de leveduras, permanecem viáveis por meses sobre superfícies bióticas ou abióticas. Diversas espécies de leveduras são encontradas em pele e mucosas de indivíduos sadios. Em estado saprofítico ainda, as leveduras encontram-se no trato gastrintestinal humano mas, a relação entre a presença desses microorganismos e sua patogenicidade está associada a diversos fatores predisponentes, tais como: número e variedade de sítios topográficos colonizados, uso prolongado de antibióticos, infecções associadas causadas por outros microorganismos e particularmente, distúrbios imunológicos ou metabólicos. Leveduras do trato gastrintestinal podem ser transmitidas, via fecal-oral diretamente ou de modo indireto, de indivíduo para indivíduo. A transmissão de uma cepa em estado saprofítico para um hospedeiro suscetível, pode resultar em colonização seguida de infecção. A gravidade do quadro clínico depende de condições do hospedeiro e características do agente etiológico que engloba fatores de virulência e resistência a antifúngicos. Esses atributos são importantes em Candida albicans na qual, enzimas com atividade de fosfolipase e proteinase são marcadores de virulência. De outro modo, fenótipos de resistência, ocorrem, com maior freqüência, em espécies não-Candida albicans. Dada a possibilidade de instalação de doença endógena e a dispersão de cepas virulentas e resistentes, a partir de colonização gastrintestinal, estudos que contribuam para a determinação desses agentes constituintes da microbiota de pacientes internados, são importantes para o conhecimento da história natural das infecções nosocomiais por leveduras. Os objetivos deste trabalho foram avaliar o trato intestinal como fonte potencial de infecção hospitalar por leveduras, descrevendo as espécies prevalentes nas primeiras horas de internação e possíveis alterações temporais, quanto a fenótipo de virulência e resistência a antifúngicos. Foram analisadas 281 amostras de leveduras isoladas de 66 crianças internadas em unidades de pediatria e semi-intensiva de hospitais públicos das cidades de São Paulo e Guarulhos, Brasil. As amostras foram isoladas de fezes coletadas nas primeiras horas de internação e durante o período de internação. A identificação das leveduras quanto a gênero e espécie foram realizadas por métodos tradicionais, analisando aspectos morfológicos e fisiológicos. A capacidade de produção de enzimas, fosfolipase e proteinase, foram verificadas conforme proposto por Price et al. 1982 e Ruchël et al., 1982. A sensibilidade aos antifúngicos: anfotericina B (AMB), fluconazol (FZ), itraconazol (IZ), cetoconazol (CZ) e nistatina (NIS) foram analisada pela técnica de difusão por discos (CECON São Paulo, Brasil). Amostras resistentes ou com sensibilidade intermediária, foram re-avaliadas pelo método de microdiluição segundo NCCL (1997) modificado por EUCAST (2002). As espécies isoladas foram: Candida tropicalis (32,7%), C.albicans (29,9%), C.parapsilosis (27, 1%), Trichosporon cutaneum e T.inkin (3,2%), Rhodotorula mucilaginosa e R.glutinis (0,7%), C.krusei (3,6%), C.guilliermondii (2,1%), C.glabrata (0,4%) e C.kefyr (0,4%). A atividade enzimática foi observada na maioria das 84 amostras de C. albicans, sendo 96% de fosfolipase e 95% de proteinase. Entre as espécies não-albicans do gênero Candida foi verificada atividade em 97% de fosfolipase e 67% de proteinase. Amostras menos sensíveis às drogas azólicas, ou seja, amostras resistentes ou com sensibilidade dependente da dose, foram encontradas em 4,3% das 281 amostras de leveduras, sendo maior porcentagem observada em C.krusei (90%). Conclui-se que existem leveduras de diversas espécies em fezes de população pediátrica hospitalizada, com fenótipos de virulência e resistência a antifúngicos. A manutenção desses fenótipos durante o período de internação pode representar fator de risco para infecção hospitalar endógena, ou ainda, fonte de dispersão de patógenos em potencial, no meio ambiente hospitalar. / At the last decades the nosocomial infections caused by yeasts raised significantly especially by Candida yeasts. The infections source can be endogen or exogenous, since spores of unicellular and multicellular are kept viable for months and several yeasts species are found in skin and mucosa of healthy people. In a saprophytic state yeasts are found in the human gastrointestinal tract but the relationship between the presence of these microorganisms and their pathology is associated with several facts such as: number, variety of sites colonized, effective use of antibiotics, associated infections caused by another microorganisms and mainly disturbance in due to lack of immunity and metabolic. Yeasts in the gastrointestinal tract can be transmitted fecal-oral direct or indirectly from an individual to another. The transmission of a strain in a saprophytic state to a host can result in colony followed by infection. The infection can be serious depending on the host conditions and the etiologic agent that includes virulent factor and resistance to antifungal drugs. These attributes are important to Candida albicans in which enzymes with phospholipase activity are responsible for virulent factors. Resistance phenotypes, otherwise it should occur more frequently in non-albicans species. Concerning the possibility of an endogen disease and the spread of virulent and resistant strains, from the gastrointestinal colony, studies that contribute to determine these agents that constitute the microbiota of patients, are important to know the natural story of nosocomial infections caused by yeasts. This work aims at evaluating the intestinal tract as a source of hospital infections by yeasts describing the remaining species in the first hours and a possible change depending on the time that may happen to virulent phenotypic and resistance to ant fungi. Two hundred eighty one yeast samples from sixty-six children attended in pediatric and semi-intensive units in 2 public hospitals located in São Paulo and Guarulhos cities in Brazil were analyzed. The fecal samples were collected at the first hours after and during their arrival at the hospital. To identify the yeasts according to their gender and species traditional methods were used, analyzing morphological and physiological aspects. The ability to produce enzymes phospholipase and proteinase was verified the same way it was proposed by Price et al. 1982 and Ruchel et al. 1982. The sensibility to antifungals: amphotericin B (AMB), f1uconazole (FZ), ketoconazole (CZ) e nistatin (NIS), was analyzed by the diffusion technical by disks (CECON São Paulo, Brazil). Resistant samples or with intermediate sensibility were confirmed by micro-dilution method according to NCCLS (1997) modified by EUCAST (2002). The isolated species were: Candida tropicalis (30%), C.parapsilosis (27%), C.krusei (4%), Trichosporon cutaneum e T.inkin (3%), Rhodotorula mucilaginosa e R.glutinis (2%), C.guilliermondii (2%), C.glabrata (1%) and C.kefyr (1%). Enzymatic activity was verified in most of the 84 C.albicans samples being 96% of phosfolipase and 95% of proteinase production. Among the non-albicans species of Candida it was observed 97% of phospholipase and 67% of proteinase activity. Less sensitive samples to azoic drugs including resistant or SDD sensibility, which depends on the achieved dose, were found in 4.3% of the 281 samples of yeast. The hugest percentage was observed in C.krusei (90%). We can conclude that different yeast species occur in stools of pediatric population hospitalized, including virulent strains and antifungal resistant phenotypes. The persistent of these phenotypes in the intestinal tract during hospitalization period may represents a risk facto r contributing to endogen infection, or play a role in dissemination of potential pathogens inside a nosocomial environment.

Os tratamentos de superfície dos implantes, por meio de adição ou subtração, tem permitido sua ativação de forma precoce com relação ao preconizado, inicialmente, por Branemark. Este trabalho constituiu-se de ensaio clínico, randomizado, controlado, duplo cego e de grupos paralelos. Avaliou-se, clinicamente, a estabilidade no pós-cirúrgico imediato e a sua evolução no período de oito semanas em implantes de mesma macrogeometria, diâmetro e comprimento em dois grupos: implantes de superfície tratada por duplo ataque ácido (grupo controle) e implantes de superfície anodizada (grupo teste). Os grupos foram avaliados quanto ao: torque de inserção, estabilidade inicial pela análise de frequência de ressonância, sua evolução no período de oito semanas e a influência do tipo ósseo na estabilidade dos grupos estudados. Foram colocados 59 implantes na maxila. Os sítios para a colocação dos implantes foram divididos aleatoriamente. Ao final do procedimento cirúrgico, foi aferido o torque de inserção e a estabilidade dos implantes por meio de análise de frequência de ressonância, com o aparelho Osstell. Esta também foi mensurada nas oito semanas seguintes à instalação. Sete implantes não atingiram o critério de inclusão para a obtenção do quociente de estabilidade do implante (ISQ). 3 do grupo controle e 2 do grupo teste apresentaram torque de inserção inferior a 20N e um de cada grupo necessitou de regeneração tecidual guiada impedindo a aferição do ISQ. Do total, 4 implantes apresentaram rotação dentro das oito semanas, o que levou à sua remoção. O grupo controle obteve torque de inserção de 45,5±18,5 Ncm e ISQ inicial de 71,6±5,5 e o grupo teste torque de inserção de 44,8±20,9 Ncm e ISQ inicial de 69,8±9,8, sendo estatisticamente similares. Essa semelhança no comportamento entre os grupos manteve-se durante todo o período de avaliação. O grupo controle atingiu, ao final de oito semanas, o ISQ médio de 70,8±6,7 e o teste de 69,7±6,0. Os resultados estatísticos demonstraram que não houve interação entre os fatores grupo e semana, entretanto, o fator semana indicou que houve variação estatística significante ao longo do tempo (p=0,003), independente do tipo de implante utilizado, com o ISQ semana 1, menor estatisticamente que todos os demais. O torque de inserção e o valor da análise de frequência de ressonância mostraram uma relação linear significante entre ambos (r=0,409, p<0,003). A média do ISQ pós-cirúrgico imediato e do torque de inserção para osso tipo II foram estatisticamente maiores que as médias para o osso tipo IV. Pode-se, assim, concluir que os grupos foram similares no que se refere a estabilidade inicial aferida tanto pelo torque de inserção quanto pela análise de frequência de ressonância, equivalência esta presente durante todo o período de oito semanas avaliado. O estudo mostrou também que a variação do tipo ósseo poderia levar a alterações na estabilidade dos implantes. / Surface treatments has allowed the loading of the implants at an early period with respect to it was recommended initially by Branemark. This study consisted of a blinded random clinical trial. It were evaluated, clinically, the stability immediate after the surgery and its evolution over the period of eight weeks in implants with the same geometry, diameter and length in two groups: dual acid etching surface (group control) and anodized surface (test group). The groups were evaluated for: insertion torque, initial stability, its evolution in the eight week period and the influence of bone type on the stability of the groups studied. 59 implants were placed in the maxilla. The sites for placement of the implants were randomly divided. At the end of the surgical procedure, it were measured insertion torque and implant stability using resonance frequency analysis (RFA), with Osstell. RFA was also measured in the eight weeks following the implant installation. Seven implants did not meet the inclusion criteria for obtaining the Implant Stability Quotient (ISQ), 3 implants, in the control group, and 2, in the test group, showed insertion torque lower than 20 Ncm and one in each group needed guided tissue regeneration which did not allow ISQ measurement. Of the total, 4 implants showed spin within eight weeks, and they were removed. The control group had insertion torque of 45.5 ± 18.5 Ncm and initial ISQ of 71.6 ± 5.5 and the test group had insertion torque of 44.8 Ncm ± 20.9 and initial ISQ of 69.8 ± 9.8, which was statistically similar. This similarity in the behavior between groups was maintained throughout the whole period of evaluation. The control group reached, in the end of eight weeks, the mean ISQ of 70.8 ± 6.7 and test reached 69.7 ± 6.0. The statistical analysis demonstrated that there was no interaction between the factors: \"group\" and \"week\"; however, the factor \"week\" indicated that there was statistically significant variation over time (p = 0.003). Independent of the type of implant used, the ISQ at first week was statistically lower than everyone else. The insertion torque and the resonance frequency analysis showed a significant linear relationship between them (r = 0.409, p <0.003). The mean ISQ, immediately after surgery, and insertion torque for bone type II were significantly higher than the averages for the bone type IV. We can conclude that the groups were similar in regard to stability measured, by the insertion torque and the initial resonance frequency analysis. Equivalence that is present throughout the eight week period of evaluation. The study also showed that depending on variation in the type of bone could lead variations in the implant stability.

Orientador: Simone Aparecida Capellini / Resumo: Objetivos: Este estudo teve por objetivos elaborar um programa de intervenção com a Técnica de Cloze e analisar a significância clínica do desempenho dos escolares com dificuldades de aprendizagem neste programa. Métodos: O programa foi elaborado a partir de uma revisão na literatura e composto por cinco níveis de dificuldade com a Técnica de Cloze. Após a elaboração, foi realizado um estudo com 28 escolares do 4º e 5º ano do ensino fundamental, divididos em Grupo I (GI): 12 sujeitos com baixo desempenho em compreensão de leitura em texto narrativo, subdivididos em GIe: 6 sujeitos submetidos à intervenção e GIc: 6 sujeitos não submetidos à intervenção; e Grupo II (GII): 16 sujeitos com baixo desempenho em compreensão de leitura em texto expositivo, subdivididos em: GIIe: 8 sujeitos submetidos à intervenção e GIIc: 8 sujeitos não submetidos à intervenção. Resultados: Foi possível elaborar um programa de intervenção com a Técnica de Cloze, baseado na literatura disponível, tendo este programa compreendido cinco níveis de dificuldades, apoiando-se nas estratégias: lexical, múltipla escolha e restringido. Os resultados da segunda fase foram analisados por meio do Método JT e a análise da significância clínica da comparação da pré e pós-testagem apontou uma mudança confiável positiva e com significância clínica para muitos sujeitos do GIe, e de forma significativa para o GIIe. Conclusão: Com base nos estudos encontrados na literatura foi possível elaborar um programa de intervençã... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Objectives: This study aimed to develop a Cloze intervention program and to analyze the clinical significance of the performance of students with learning difficulties in this program. Methods: The program was elaborated from a review in the literature and was composed of five levels of difficulty with the Cloze intervention program. After the elaboration, a study was carried out with 28 students from the 4th and 5th grades of elementary school, divided into: Group I (GI): 12 subjects with poor reading comprehension in narrative text, subdivided into GIe: 6 subjects submitted to intervention and ICG: 6 subjects not submitted to intervention. Group II (GII): 16 subjects with poor reading comprehension in expository text, subdivided into: GIIe: 8 subjects submitted to intervention and GIIc: 8 subjects not submitted to intervention. Results: It was possible to elaborate a Cloze intervention program based on the available literature, being that this program comprised five levels of difficulties based on the strategies: lexical, multiple choice and restricted. The results of the second phase were analyzed using the JT method and the analysis of the clinical significance of the pre and posttest comparison showed a positive and clinically significant change for many subjects of GI and significantly for GIIe. Conclusion: Based on studies found in the literature, it was possible to elaborate a Cloze intervention program for reading comprehension. The elaborated program presented clini... (Complete abstract click electronic access below) / Mestre

Obstacles sometimes limit enrollment in randomized clinical trials of an exper- imental product versus an active control, making it desirable to augment the ran- domized control group with historical control groups. However, bias between control groups with respect to the mean outcome could lead to spurious conclusions. Meth- ods are necessary that allow for the combination of control groups while controlling for bias. Pocock (1976) developed a Bayesian test to address this need, but it requires sub- jective specification of the variance of the bias between the randomized and historical control groups and is designed to include only a single historical control group. In the context of an actively controlled non-inferiority trial, we extend his method on three fronts. First, we replace subjective specification of the variance of the bias with empirically driven estimates. Second, we develop an adaptive design that re-powers a trial based on an interim estimate of the variance of the bias using observed data. Third, we modify the test to include multiple historical control groups. When including a single historical control group, simulations show that the true bias, if known, can be used in place of the variance of the bias, and that this estimate ivmaintains Type I Error with no loss in power as compared to using the true variance of the bias. Further, we show that using an empirical estimate of the bias to estimate the variance of bias may result in moderately inflated Type I Error, but that using a conservative estimate of the bias (the upper bound of a 90% confidence interval) maintains Type I Error. Simulations also demonstrate that using an estimate of the bias at the interim and conclusion provides designed power but may result in moder- ately inflated Type I Error. Therefore, a conservative estimate of the bias should be used at trial end when using this approach. Lastly, it is shown that if an adequate number of multiple historical control groups are available, the modified test maintains Type I Error when using bias estimates. These methods provide objective guidance on parameter estimation, but further research is necessary in order to improve power.

Objetivos: O objetivo deste ensaio clínico randomizado foi avaliar o comportamento de restaurações de resina composta bulk-fill em dentes posteriores (classes I e II). Metodologia: Dezessete pacientes que necessitavam de restaurações em pelo menos dois dentes posteriores foram selecionados para participar do estudo. As causas para indicação das restaurações foram: substituição de restauração deficiente de amálgama ou resina composta e/ou lesão de cárie. Em cada paciente foram realizadas duas restaurações. Randomicamente, uma cavidade foi restaurada com a resina nanohíbrida Esthet-X HD (grupo controle) e a outra restaurada com a resina Esthet-X HD associada à resina de baixa contração Surefil SDR Flow (grupo teste). Em ambos os grupos, um sistema adesivo convencional de dois passos (XP Bond) foi utilizado. Todos os pacientes receberam tratamento global para a atividade cariosa. Após um período de quatro anos, a qualidade das restaurações foi avaliada por 1 examinador previamente calibrado, através de uma modificação do método USPHS e através do método FDI. Os dados obtidos foram submetidos à análise estatística pelo teste não-paramétrico Mann-Whitney (p<0,05) e a concordância intra-observador avaliada através de teste Kappa. Resultados: No quarto ano de acompanhamento, 26 dentes (18 restaurações classe I e 8 classe II) foram avaliadas, e não foram observadas diferenças estatisticamente significantes entre as restaurações dos grupos controle e teste para os métodos de avaliação utilizados. Não houve falhas em nenhuma das restaurações ao longo do tempo. Conclusão: A qualidade das restaurações classe I e II com resina bulk-fill foi semelhante à das restaurações com resina nanohíbrida convencional. A técnica com resina bulk-fill mostrou bom desempenho clínico tão bom quanto a convencional durante os 4 anos de acompanhamento. / Objectives: The objective of this randomized clinical trial was to evaluate the behavior of bulk-fill composite restorations in posterior teeth (classes I and II). Methodology: Seventeen patients who required restorations on at least two posterior teeth were selected to participate in the study. The causes for indication of restorations were: replacement of deficient amalgam or composite resin restoration and/or caries lesion. In each patient, two restorations were performed. Randomly, one cavity was restored with Esthet-X HD nanohybrid composite (control group) and the other was restored with Esthet-X HD resin associated with the bulk-fill composite Surefil SDR Flow (test group). In both groups, a two-step total-etch adhesive system (XP Bond) was used. All patients received global treatment for carious activity. After a period of four years, the quality of the restorations was evaluated by a previously calibrated examiner, through a modification of the USPHS method and through the FDI method. The data were submitted to statistical analysis by the non-parametric Mann-Whitney test (p <0.05) and the intra-observer agreement was evaluated by Kappa test. Results: At the 4-year follow-up, 26 teeth (18 class I and 8 class II restorations) were evaluated, and no statistically significant differences between control and test groups were observed for both evaluation methods used. There were no failures in any of the restorations over time. Conclusion: The quality of class I and II restorations with bulk-fill resin was similar to that of conventional nanohybrid resin. The bulk-fill composite technique showed good clinical performance as well as the conventional one during the 4 years of follow-up.

BACKGROUND and AIMS. Patellofemoral pain syndrome (PFPS) is complex and challenging musculoskeletal disorder. Maltracking of the patella is considered to be one of the primary causative factors. Vastus Medialis Oblique (VMO) and Vastus Lateralis (VL) muscle imbalance in terms of EMG magnitude and timed onset is implicated in either initiating or perpetuating the patellofemoral pain (Cowan et al, 2002, Witvrouw et al, 1996). Many physiotherapeutic treatments are aimed at addressing this muscle imbalance despite a lack of evidence confirming or refuting it exists and it's association with pain and function. The ultimate aim of the study was therefore to establish if it is appropriate to continue treating muscle imbalance in patients with clinically defined PFPS. OBJECTIVES. The overall objectives of the study were to establish: 1. If VMO-VL muscle imbalance exists in PFPS patients and if so is it specific to this condition or does a similar VMO-VL muscle imbalance exists in a healthy population? 2. If muscle imbalance does exist is it related to clinical symptoms used as indications of pain syndrome in clinical practice? 3. Is muscle imbalance associated with lower limb muscle physiology i.e. lower limb and quadriceps muscle strength in both fresh and fatigued states. METHODS. The study employed a cross-sectional design. 63 patients with patellofemoral pain syndrome (PFPS) and 63 age/sex matched healthy subjects were recruited and VMO & VL normalised EMG RMS amplitude and time onset differences were assessed during functional and experimental tasks. Additionally, correlations with pain level, functional status, muscular flexibility and biomechanical characteristics of the lower limb were explored. RESULTS. The results revealed that the VMO-VL activation patterns are task specific and most significantly related to functional stepping down task at a fast speed of execution (p=0.000). This interesting link between the type of muscle contraction, the speed of execution and the recruitment pattern of the VMO-VL was also confirmed by the non-functional isokinetic eccentric contraction (p=0.000). Additionally, it is the timing of the VMO-VL activation rather the intensity that is important. Also, a correlation appears to exist between activation pattern and duration of symptoms and knee functional performance (p=0.03) but not with the level of pain. CONCLUSION. The findings of the study suggest that the VMO-VL muscle imbalance does exist in a clinically defined PFPS population. Unlike previous studies however, this thesis suggests that specificity of the functional activities and speed of execution have a significant role to play in the muscular performance and it could be argued that this translates to a role in PFPS. It would therefore seem appropriate to continue addressing and treating this complex and challenging issue with physiotherapeutic interventions but this may need to be targeted to interventions that are tailored to addressing issues in relation to stepping down and at fast speed.

BACKGROUND: Adjudication is a standardized, objective, and often blinded mechanism designed to assess clinical events with increased accuracy. It is performed by a centralized committee of independent reviewers, who are specialized, expert physicians who have no involvement with either the treatment of study subjects or the trial sponsor. Adjudication can decrease variability and bias in study results and increase the likelihood of correct identification, assessment, and categorization of clinical events such as potential malignancies diagnosed through histopathology. Histopathology is highly variable due to the subjective nature of the assessments. THESIS: If it is the case that there are clinically significant discrepancies between local and central diagnoses and that central adjudication yields more accurate diagnoses than a local pathologist, then it should be accepted that adjudication ought to be more widely used in clinical trials to assess histopathology-related safety outcomes and endpoints. METHODS AND STATISTICS: This is a retrospective cross-sectional study assessing interrater variability between local and central diagnoses of biopsy samples in a clinical trial setting using kappa scores and percent agreement. Certified Professional Coders (CPC) and central pathologists used the International Classification of Diseases for Oncology revision 3 (ICD-O 3) to codify the local and central assessments to permit comparison. Three statistical groups (group A: the full dataset, group B: pathology sub-specialty reading groups, and group C: non-melanoma skin cancers versus all other malignancies) were assessed for interrater variability in seven separate analyses: neoplasm versus non-neoplasm (analysis 1), benign versus malignant including non-neoplasms (analysis 2.1), benign versus malignant excluding non-neoplasms (analysis 2.2), discrepancies in morphology and/or behavior including non-neoplasms (analysis 3.1), discrepancies in morphology and/or behavior excluding non-neoplasms (analysis 3.2), all discrepancies leading to differences in treatment (analysis 4.1), and all discrepancies leading to difference in treatment with round 1 matches removed (analysis 4.2). RESULTS: 602 cases comprised the dataset. Based on kappa scores, there is near perfect agreement between the central and local lab diagnoses in analyses 1, 2.1, and 2.2 in group A (all cases in the dataset). The percent agreement for these analyses is above 90%. The group A (full dataset) kappa score and percent agreement decreased to 0.59 and 68.3%, respectively, in analysis 3.1 (discrepancies in morphology and/or behavior codes, including non-neoplasms). When non-neoplasms were removed (analysis 3.2), the kappa score and percent agreement were 0.52 and 57.0%, respectively. In group C, NMSC had substantial kappa agreement in analyses 1, 2.1, and 2.2, whereas all other malignancies had near perfect kappa agreement. All percent agreements were above 88% and surpassed the minimally acceptable threshold for interrater percent agreement in healthcare (80%). Group B divided the data set into 10 sub-specialty reading groups. Kappa scores ranged from 0.66 (GYN) to 1.00 (lung) in analysis 1; the analysis 1 kappa score for lymphoma was 0.55, but this was not statistically significant. In analysis 2.1, lung and sarcoma had the highest kappa scores (1.00) and dermatology and GYN had the lowest (0.71). As in analysis 1, the kappa score for lymphoma was 0.55 but was not statistically significant. When non-neoplasms were removed from analysis 2.2, 6 of the 10 sub-groups had kappa scores of 1.00, but all 6 had sample sizes less than 10. Percent agreement ranged from 80 to 100 percent. When all cases were considered regardless of number of rounds of review (analysis 4.1), about 90% of diagnoses would have similar courses of treatment. All sub-groups except sarcoma reached the minimally acceptable agreement rate in healthcare (80%). In the remaining 33% of cases that did not have matching diagnoses in round 1 (analysis 4.2), 34% may have different courses of treatment depending on whether the local or central diagnoses was used. Mid-study updates to the charter and CPC/reviewer manuals and processing of specimens did not have a significant impact on results. CONCLUSION: Although there is little discrepancy between local and central pathologists on whether malignancies exist among samples, there is discord regarding specific diagnoses and their associated treatments. Adjudication can assist in decreasing this discordance in order to develop the most specific and accurate safety profile for a compound.

Adolescents and young adults (AYAs) ages 15-39 with cancer have experienced stagnant survival rates for the past 30 years in comparison to those older or younger diagnosed with cancer. Survival disparities for this population may be due to biologic factors, lack of consistent and effective access to care, and unique psychosocial needs of this age group, and taken together, present an opportunity for health policy intervention. Of particular interest are barriers most important to AYAs themselves, appropriate and timely clinical trial enrollment, and the ability to preserve fertility prior to initiating treatment. These barriers may be more difficult to overcome for AYAs that are from rural areas, those that may be un- or under- insured, of lower socioeconomic status or educational attainment, and other social determinant of health related-factors. In this dissertation, I examined the factors that drive the challenges encountered by AYAs with cancer and discuss potential solutions to overcome these challenges. The first aim of this dissertation establishes which challenges or aspects of the cancer experience are most important to AYAs using a mixed methods approach. The second and third aims build off of challenges identified in aim one using quantitative methods. In aim two, AYA clinical trial enrollment in the United States is examined using a nationally-representative sample with a specific focus on rural disparities. In aim three, historical utilization of fertility preservation consultations and procedures are studied among AYAs treated a single institution serving a rural population.

A key component of informed consent to participate in research is the understanding that research is not the same as treatment and that scientific goals have priority over therapeutic ones. However, studies have found many research participants do not understand these important differences between research and treatment, a phenomenon termed therapeutic misconception (TM). The problem addressed in this project was research nurses' lack of education regarding the existence and concepts of TM, and their struggles to assess and address research participants' TM of clinical trials. Matutina's conceptual model of TM was used to guide this project. The purpose of this project was to develop an educational program that prepares registered nurses to assess clinical trials participants for TM and correct any misunderstandings. The educational program included concepts related to TM, guidance on recognizing TM, strategies to correct participant misunderstanding, and assessments of nurses' understanding of related concepts and strategies. The products of this project include the program with an implementation plan and an evaluation plan that outlines short- intermediate- and long- term plans for evaluating effectiveness of this program. For both short and intermediate-term evaluation, outcomes will be measured using a pre and post survey. The long-term evaluation of the educational program was designed as a study to measure TM among research participants comparing data before and after nurses receive TM education. Refining the standard education of TM for registered nurses can serve both to improve protection of trial participants and to clarify the informed consent process, ultimately contributing to a more informed population of clinical trials participants.

Thesis (M.Ing. (Electrical Engineering))--North-West University, Potchefstroom Campus, 2007.