Das Ziel der vorliegenden randomisierten, klinisch kontrollierten, prospektiven Studie war es, die Leistungsfähigkeit des Universaladhäsivs 3M™ Scotchbond™ Universal (SBU) bei dessen Anwendung an nicht kariösen Zahnhalsläsionen (NCCL) klinisch und mit optischer Kohärenztomografie (OCT) zu bewerten. An 55 Patienten wurde das Universaladhäsiv in den Konditionierungsmodi self-etch (SE, n = 55), selective-enamel-etch (SEE, n = 55) und etch-and-rinse (ER, n = 55) in Kombination mit dem Komposit Filtek™ Supreme XTE angewendet. Das etablierte Etch-and-rinse-Adhäsiv OptiBond™ FL (OFL) diente als Referenzsystem (n = 55). Die Restaurationen wurden nach 14 Tagen (Baseline), sechs und 12 Monaten klinisch untersucht (FDI-Kriterien). Parallel dazu erfolgte die quantitative Bewertung der interfazialen Spaltformationen am Schmelz und Dentin/Zement mit OCT, welche erstmals bereits direkt nach Füllungslegung vorgenommen wurde. Die kumulativen Fehlerraten (CFR), die klinischen Parameter Randverfärbung, Randadaptation und Frakturen/Retention, sowie die gemittelten adhäsiven Defekte pro Gruppe wurden statistisch ausgewertet. Nach 12 Monaten ergaben sich in allen Gruppen mit SBU signifikant geringere kumulative Fehlerraten als in der Kontrollgruppe OFL. Unmittelbar nach Füllungslegung sowie nach sechs und 12 Monaten konnten an der Schmelz-Komposit-Interface in der Gruppe SBU/SE mehr adhäsive Defekte als in den Gruppen SBU/SEE und OFL nachgewiesen werden. An der dominierenden Dentin/Zement-Komposit-Interface zeigte sich hingegen in der Gruppe OFL generell ein signifikant höheres Verbundversagen. Sowohl die klinische als auch die tomografische Bewertung ergaben ein geringeres Verbundversagen in den Gruppen mit SBU im Vergleich zu OFL. Dabei resultierte auch aus der unbeabsichtigten Phosphorsäureätzung am Dentin bei selektiver Schmelzätzung kein Nachteil. Mit OCT konnten signifikante Gruppenunterschiede früher als mit der klinischen Bewertung, nämlich bereits unmittelbar nach Füllungslegung, dargestellt und reproduziert werden. Das verdeutlicht die hohe Sensitivität und Reliabilität der Methode zur Bewertung des Zahn-Komposit-Verbundes und lässt sehr viel frühere Aussagen zur klinischen Bewährung von Systemen zur Restauration mit Kompositen zu.

Sun exposure is implicated in the majority of skin cancer cases so it is important to identify interventions that successfully decrease young people's tanning behaviors and increase their sun protection behaviors. Research suggests that interventions that focus on the more immediate appearance related effects of tanning, rather than on future health risks, may be more effective in altering UV-related behaviors. Dissonance induction is a strategy that has been used to successfully alter other health-related behaviors. This study sought to determine if a dissonance induction intervention might be similarly successful in changing UV-related behaviors. The study yielded mixed findings. Relative to a healthy lifestyle control condition, the tanning condition resulted in a decrease in intentions to tan indoors and in actual number of hours spent sunbathing. The tanning condition also resulted in an increase in intentions to use sunscreen on the body. However, compared to a psycho-educational control condition, both groups seemed to have been equally successful and unsuccessful on different measures of UV-related behaviors and intentions. The findings of this study suggest that a dissonance induction intervention for tanning may be successful, but that it requires further study. Despite the mixed findings, this study serves as an important step in the search for successful interventions for decreasing tanning behaviors and increasing sun-protection behaviors.

Orientador: Carlos Rossa Júnior / Resumo: Curcumin é o principal composto biologicamente ativo extraído do rizoma da espécie Curcuma longa. Diversos estudos relatam efeitos biológicos do curcumin que são de interesse em diferentes condições clínicas, como doenças inflamatórias intestinais, artrite reumatóide, câncer, diabetes, obesidade, depressāo, líquen plano e periodontite. Estudos pré-clínicos em modelos de periodontite experimental consistentemente demonstram efeito anti-inflamatório com a redução da reabsorção óssea. No entanto, existem poucas informações sobre o efeito biológico do curcumin no reparo dos tecidos periodontais, uma vez que na maioria dos estudos pré-clínicos a administração do curcumin é feita como único tratamento e de forma concomitante à indução da doença. Estudos clínicos do uso do curcumin como adjuvante do tratamento periodontal mecânico relatam, em geral, efeitos benéficos; porém há necessidade de avaliação sistemática dos resultados e da validade interna e externa dos trabalhos clínicos. Este trabalho tem o objetivo geral de investigar o potencial do curcumin aplicado localmente como adjuvante do tratamento periodontal mecânico no reparo dos tecidos periodontais. A hipótese é que a aplicação local de curcumin potencializa seus efeitos biológicos favorecendo o reparo tecidual ao evitar as dificuldades associadas às pobres propriedades farmacocinéticas da administração oral. O trabalho está organizado em três estudos: (i) estudo pré-clínico em modelo de periodontite experimental com aplica... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Curcumin is the main biologically active compound extracted from the rhizome of the Curcuma longa. Several studies report biological effects of curcumin that are of interest in different clinical conditions, such as inflammatory bowel diseases, rheumatoid arthritis, cancer, diabetes, obesity, depression, lichen planus and periodontitis. Pre-clinical studies in experimental periodontitis models consistently demonstrate an anti-inflammatory effect by reducing bone resorption. However, there is limited information on the biological effect of curcumin in repairing periodontal tissues, since in most preclinical studies curcumin is administered as the sole treatment and concurrently with the induction of the disease. Clinical studies using curcumin as an adjunct to mechanical periodontal treatment report, in general, beneficial effects; however, there is a need for systematic evaluation of the results and the internal and external validity of clinical studies. This work aims to investigate the potential of locally-delivered curcumin as an adjunct to mechanical periodontal treatment in the repair of periodontal tissues. The hypothesis is that local application of curcumin enhances its biological effects, favoring tissue repair by avoiding issues associated with the poor pharmacokinetic properties of oral administration. The work is organized in three studies: (i) pre-clinical study in an experimental periodontitis model with local application of curcumin as an adjunct to mechanical ... (Complete abstract click electronic access below) / Doutor

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The placebo response can affect inference in analysis of data from clinical trials. It can bias the estimate of the treatment effect, jeopardize the effort of all involved in a clinical trial and ultimately deprive patients of potentially efficacious treatment. The Sequential Parallel Comparison Design (SPCD) is one of the novel approaches addressing placebo response in clinical trials. The analysis of SPCD clinical trial data typically involves classification of subjects as ‘placebo responders’ or ‘placebo non-responders’. This classification is done using a specific criterion and placebo response is treated as a measurable characteristic. However, the use of criterion may lead to subject misclassification due to measurement error or incorrect criterion selection. Subsequently, misclassification can directly affect SPCD treatment effect estimate. We propose to view placebo response as an unknown random characteristic that can be estimated based on information collected during the trial. Two strategies are presented here. First strategy is to model placebo response using criterion classification as a starting point or the observed data, and to include the placebo response estimate into the treatment effect estimation. Second strategy is to jointly model latent placebo response and the observed data, and estimate treatment effect from the joint model. We evaluate both strategies on a wide range of simulated data scenarios in terms of type I error control, mean squared error and power. We then evaluate the strategies in presence of missing data and propose a method for missing data imputation under the non-informative missingness assumption. The data from a recent SPCD clinical trial is used to compare results of the proposed methods with reported results of the trial. / 2018-01-01T00:00:00Z

In adaptive design clinical trials, an endpoint at the final analysis that takes a long time to observe is not feasible to be used for making decisions at the interim analysis. For example, overall survival (OS) in oncology trials usually cannot be used to make interim decisions. However, biomarkers correlated to the final clinical endpoint can be used. Hence, considerable interest has been drawn towards the biomarker informed adaptive clinical trial designs. Shun et al. (2008) proposed a "biomarker informed two-stage winner design" with 2 active treatment arms and a control arm, and proposed a normal approximation method to preserve type I error. However, their method cannot be extended to designs with more than 2 active treatment arms. In this dissertation, we propose a novel statistical approach for biomarker informed two-stage winner design that can accommodate multiple active arms and control type I error. We further propose another biomarker informed adaptive design called "biomarker informed add-arm design for unimodal response". This design utilizes existing knowledge about the shape of dose-response relationship to optimize the procedure of selecting best candidate treatment for a larger trial. The key element of the proposed design is that, some inferior treatments do not need to be explored and the design is shown to be more efficient than biomarker informed two-stage winner design mathematically. Another important component in the study of biomarker informed adaptive designs is to model the relationship between the two endpoints. The conventional approach uses a one-level correlation model, which might be inappropriate if there is no solid historical knowledge of the two endpoints. A two-level correlation model is developed in this dissertation. In the new model a new variable that describes the mean level correlation is developed, so that the uncertainty of the historical knowledge could be more accurately reflected. We use this new model to study the "biomarker informed two-stage winner design" and the "biomarker informed add-arm design for unimodal response". We show the new proposed model performs better than conventional model via simulations. The concordance of inference based on biomarker and primary endpoint is further studied in a real case.

Indiana University-Purdue University Indianapolis (IUPUI) / Phase I clinical trials (P1Ts) are the first step in testing new medical therapies in humans, and are essential for developing new and innovative therapies for children with cancer. P1Ts are ethically controversial as they are not intended to directly benefit participants, but are particularly controversial for children with cancer who are only able to participate when there is no known curative therapy for their cancer. Benefits of pediatric oncology P1T participation may include improved quality of life (QOL) and hope. Risks may include fostering unrealistic hope, burdening children with additional medical procedures and toxicities, and limiting the opportunity for palliation. The goal of this dissertation was to investigate the P1T participation experience for children with cancer and their parents by: (1) assessing what is currently known about the participation experience, (2) exploring ways to understand and assess treatment burden and QOL during participation, and (3) interviewing parents about the experience of having a child participate in a P1T. Following a review of the literature, two studies were conducted: a longitudinal pilot study of 13 parent and child dyads who enrolled in a pediatric oncology early phase clinical trial at the recruiting institution, and a phenomenological study of 11 parents of children with cancer who participated in pediatric oncology P1Ts. Key findings included a dearth of research on the experiences of children and parents in pediatric oncology P1Ts. Instead, existing research has focused on consent processes. The longitudinal pilot study provided some insight into experiences of children and parents during trial participation, including that there may be time points when parents’ and children’s perceptions of the child’s quality of life substantively differ. Interviews with parents confirmed some of the anticipated benefits and risks of participation in P1Ts, and highlighted parents’ sense of running out of time to find an effective treatment and needing to use time they have with their child well. Specific challenges in conducting this research were participant attrition due to disease progression and the need for multi-site research to obtain an adequate sample.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第12801号 / 論医博第2073号 / 新制||医||1001(附属図書館) / 80845 / 京都大学大学院薬学研究科創薬科学専攻 / (主査)教授 川上 浩司, 教授 松原 和夫, 教授 今中 雄一 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第20289号 / 社医博第78号 / 社新制||医||9(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 山田 亮, 教授 中山 健夫, 教授 古川 壽亮 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

Indiana University-Purdue University Indianapolis (IUPUI) / Currently, the predominant view in research ethics maintains that physicians can morally justify offering randomized clinical trial enrollment to their patients only if some form of equipoise is present. Thus, the physician must experience (either individually or communally) a state of reasoned uncertainty concerning the relative merits of two or more competing treatments for a given disease before she may recommend that her patient participate in a clinical trial. Increasingly, however, this position has been subject to critical attention and considerable negative scrutiny. My argument engages this trend by turning to the history of philosophy; here I claim that the use of the term “equipoise” in the medical research context is extremely similar to terms and concepts from the philosophical tradition of skepticism, and as a result of this similarity it is possible to understand the principle of equipoise’s vulnerability to already published criticisms. A comparison of the criticisms of equipoise within the medical research literature to criticisms of philosophical skepticism reveals a potentially grim future for equipoise as a legitimate guiding principle for the ethical conduct of clinical research.