Thesis (M.S.)--Brigham Young University. Dept. of Statistics, 2007. / Includes bibliographical references (p. 57-60).

Thesis (M.Med.Sc.)--University of Hong Kong, 2003. / Also available in print.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2003. / Bibliography: leaves 109-112. Also available online.

Thesis (Ph.D.)--Ohio University, March, 2004. / Title from PDF t.p. Includes bibliographical references (p. 145-155)

Thesis (Ph.D.)--University of Alberta, 2009. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Experimental Medicine, Department of Medicine, Faculty of Medicine & Dentistry. Title from pdf file main screen (viewed on November 21, 2009). Includes bibliographical references.

Introduction. Les ultrasons (US) basse fréquence appliqués sur la peau pour en augmenter laperméabilité (sonophorèse) peuvent promouvoir le passage transcutané de molécules in vitroet in vivo chez l’animal. L’objectif de ce travail a été d’appliquer la sonophorèse à l’homme invivo.Méthodes. Trois essais cliniques randomisés ont été menés chez le volontaire sain : l’essai (1)évaluant la tolérance des US à différentes intensités versus placebo ; l’essai (2) évaluant lapénétration transcutanée de l’histamine après sonophorèse ; l’essai (3) comparant l’effetvasoconstricteur d’un dermocorticoïde sans et après sonophorèse. Les US étaient délivrés enmode pulsé, avec une sonde de 36 kHz, durant 5 minutes, à des intensités de 1,57 à 3,50W/cm2.Résultats. Dans l’essai (1), aucune toxicité (douleur > 40/100 ou nécrose) n’a été observéechez les 34 sujets inclus. Les effets secondaires étaient un érythème, et des acouphènesrégressifs dès l’arrêt des US. Dans l’essai (2), l’histamine a induit une papule chez 9/10 sujets,uniquement sur les zones préalablement traitées par US. Dans l’essai (3), sur les 15 sujets, lavasoconstriction induite par le dermocorticoïde était significativement plus importante sur leszones traitées par US, surtout avec une occlusion longue (2h).Conclusions. Ces essais démontrent qu’avec des intensités ultrasonores bien tolérées chezl’homme, la sonophorèse est efficace pour faire pénétrer l’histamine et améliorer l’efficacitédes dermocorticoïdes. / Introduction. Low-frequency ultrasound (US) applied on skin, called sonophoresis, havebeen investigated to enhance the transdermal transport of various drugs in vitro and in vivo inanimals. We aimed to investigate low-frequency sonophoresis in vivo in humans.Methods. Three randomized clinical trials have been conducted in healthy subjects: trial (1)aimed to assess skin toxicity of sonophoresis at different intensity levels compared to placebo;trial (2) aimed to investigate the transdermal penetration of histamine with sonophoresis; trial(3) aimed to investigate the clinical efficiency of sonophoresis in enhancing transdermalpenetration of topical steroids in human skin. US were applied in pulsed mode for 5 minutes,with a 36 kHz device. US intensities ranged from 1.57 to 3.50 W/cm2.Results. In trial (1), no toxicity, defined as a pain score > 40/100 or necrosis, was reported.The most frequent adverse events were erythema, and tinnitus, which ceased ondiscontinuation of US. In trial (2), arm zones without US showed no papules, whereas 9/10subjects receiving US showed papules. In trial (3), including 15 subjects, vasoconstrictionwas significantly higher with the topical steroid applied after US than without US, especiallyin the zone with 2-h occlusion.Conclusions. These clinical trials provide favourable exploratory results regarding toleranceof low-frequency sonophoresis on human skin in vivo. They confirm that sonophoresisenhances transdermal penetration of histamine and increases the efficiency of topical steroids.

As most adaptive clinical trial designs are implemented in stages, well-understood methods of sequential trial monitoring are needed. In the frequentist paradigm, examples of sequential monitoring methodologies include the p-value combination tests, conditional error, conditional power, and alpha spending approaches. Within the Bayesian framework, posterior and predictive probabilities are used as monitoring criteria, with the latter being analogous to the conditional power approach. In a placebo or active-contolled dose response clinical trial, we are interested in achieving two objectives: selecting the best therapeutic dose and confirming this selected dose. Traditional approach uses the parallel group design with Dunnett's adjustment. Recently, some two- stage Seamless II/III designs have been proposed. The drop-the-losers design considers selecting the dose with the highest empirical mean after the first stage, while another design assumes a dose-response model to aid dose selection. These designs however do not consider prioritizing the doses and adaptively inserting new doses. We propose an adaptive staggered dose design for a normal endpoint that makes minimal assumption regarding the dose response and sequentially adds doses to the trial. An alpha spending function is applied in a novel way to monitor the doses across the trial. Through numerical and simulation studies, we confirm that optimistic alpha spending coupled with informative dose ordering jointly produce some desirable operating characteristics when compared to drop-the-losers and model-based Seamless designs. In addition, we show how the design parameters can be flexibly varied to further improve its performance and how it can be extended to binary and survival endpoints. In a biosimilarity trial, we are interested in establishing evidence of comparable efficacy between a follow-on biological product and a reference innovator product. So far, no standard method for biosimilarity has been endorsed by regulatory agency. We propose a Bayesian hierarchical bias model and a non-inferiority hypothesis framework to prove biosimilarity. A two-stage adaptive design using predictive probability as early stopping criterion is pro- posed. Through simulation study, the proposed design controls the type I error better than the frequentist approach and Bayesian power is superior when biosimilarity is plausible. Two-stage design further reduces the expected sample size.

1 Abstract Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacognosy Student: Olga Krupová Supervisor: PharmDr. Tomáš Siatka, CSc. Title of diploma thesis: Modern phytotherapy - revision of usage of medicinal plants according to clinical trials Key words: phytotherapy, medicinal plants, liver diseases, painful joints, nervousness and insomnia, clinical trials The aim of diploma thesis was to review the said effects of the herbs, to make a list of herbs used in popular traditional medicine of selected diseases and to verify their use by giving documented evidence. This thesis addresses in detail three ranges of problems in which the use of herbal therapy could be considered. Following three ranges of problems were selected: liver diseases, painful joints, nervousness and insomnia. Clinical studies were explored to substantiate the effects of individual herbs or their substances. Preclinical studies were used in case of deficiency in clinical studies. The outcome of this thesis was to approve or - on the contrary - to disapprove the effects quoted by the use of folk medicine herbs. From the result of this thesis it emerges, that not all popular quoted herbal indications are verified by sufficient evidence. However, for a considerable part of the quoted herbs their effects were...

Made available in DSpace on 2014-06-11T19:31:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-09-02Bitstream added on 2014-06-13T20:22:07Z : No. of bitstreams: 1 000737133.pdf: 1925086 bytes, checksum: f98f5f34cf11968cab162e816bf69d5b (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O objetivo desse estudo foi avaliar através das análises clínica e clínica/digital o comportamento de 90 restaurações, realizadas em lesões cervicais não cariosas, após 12 e 24 meses de suas realizações. Foram formados 3 grupos de estudo com 30 dentes cada, de acordo com os materiais e técnicas empregadas. Os dentes pertencentes ao grupo I receberam, após o condicionamento com ácido fosfórico 35% em esmalte e dentina, o sistema adesivo convencional Peak LC Bond (Ultradent Products, Inc., South Jordan, USA); os do grupo II receberam a aplicação do sistema adesivo autocondicionante Clearfil Protect Bond (Kuraray Medical Inc., Kurashiki, Okayama, Japão); os do grupo III, previamente à aplicação do sistema adesivo autocondicionante Clearfil Protect Bond (Kuraray Medical Inc., Kurashiki, Okayama, Japão), receberam o condicionamento com ácido fosfórico apenas em esmalte. Todos os dentes foram restaurados com a resina composta Amelogen Plus (Ultradent Products, Inc., South Jordan, USA). Após o acabamento e polimento, bem como aos 12 e 24 meses, as restaurações foram fotografadas para posterior análise clínica/digital em computador de alta resolução. De acordo com critérios previamente estabelecidos, dois examinadores devidamente calibrados realizaram as análises clínica e clínica/digital das restaurações, nos tempos inicial, 12 e 24 meses de suas realizações. Para a análise clínica das restaurações foram considerados as variáveis retenção, adaptação marginal, descoloração marginal, presença de lesão de cárie e sensibilidade, enquanto que para a clínica/digital, retenção e descoloração marginal. Para análise estatística foram aplicados os testes de Kruskal-Wallis, de Wilcoxon, de Friedman e de Dunn. Aos 12 e 24 meses de análise clínica e clínica/digital não foram observadas diferenças estatisticamente significativas para as variáveis analisadas... / The aim of this study was to evaluate the performance of 90 restorations performed in noncarious cervical lesions through clinical and clinica/digital analysis after 12 and 24 months. Three groups were obtained with 30 teeth each, according to the materials and techniques. The teeth of group I received, after etching with 35% phosphoric acid on enamel and dentin, the total-etch adhesive system Peak LC Bond (Ultradent Products, Inc., South Jordan, USA); the teeth of group II received the self-etching adhesive system Clearfil Protect Bond (Kuraray Medical Inc., Kurashiki, Okayama, Japão), and the teeth of group III, prior to application of the self-etching adhesive system Clearfil Protect Bond (Kuraray Medical Inc., Kurashiki, Okayama, Japão), received the phosphoric acid etching only in enamel. All teeth were restored with composite resin Amelogen Plus (Ultradent Products, Inc., South Jordan, USA). Two calibrated examiners performed the clinical and clinical/digital analysis of the restorations at baseline, 12 and 24 months. For clinical analysis were considered the factors: retention, marginal adaptation, marginal discoloration, presence of caries and sensitivity; while for the clinical/digital analysis only retention and marginal discoloration. At 12 and 24 months of clinical and clinical/digital analysis, there were no statistically significant differences for the variables analyzed among the study groups, as well as within a group in said analysis time. The dental sensitivity significantly decreased and was totally eliminated after 12 and 24 months of clinical analysis, respectively. In the statistical analysis were applied the Kruskal-Wallis, Wilcoxon, Friedman and Dunn tests. We conclude according the clinical and clinical/digital analysis that non-carious cervical lesions restorations, performed with total-etch and self-etching adhesive systems, showed satisfactory and similar clinical performance at 12 and 24 months of analysis.

Introduction: Breast cancer is the most frequent cancer among women worldwide. Breast cancer treatments and treatment-related factors (type, dose, duration, and side-effects) have been found to be associated with weight gain in women. Overweight and obesity, in breast cancer survivors, is associated with increased risk of breast cancer-specific and all-cause mortality. Prognosis may be improved by maintaining a healthy weight but research in weight management in women treated for breast cancer is relatively limited. Aim: To design a weight loss trial for women treated for breast cancer and to evaluate its feasibility, and effect on body weight and quality of life (QoL). Methods: The development and evaluation of the trial was guided by the Medical Research Council framework for developing and evaluating complex interventions and involved mixed methods research. The development involved a systematic review of 13 randomised controlled trials (RCTs) targeting weight loss in women treated for breast cancer, and a mixed methods study [focus group meetings (n= 15), survey (n= 139), and interviews (n=20)] with the target population to understand their experiences and future preferences of a weight loss programme. The findings of these preliminary studies informed the design of a feasibility RCT of weight loss intervention. Results: 45 women (age 41-89 y; BMI 25.1–66.2 kg/m2) previously treated for breast cancer were randomly allocated to three groups: Weight Watchers vouchers for 12 weeks plus 5 dietitian-led support groups (WW plus: n=14); Weight Watchers vouchers only (WW: n=16) or waiting-list control (Weight Watchers vouchers after 3 months) (controls: n=15). Weight and QoL were measured at 0 and 12 weeks and data was available for 38 (84%) participants at 12 weeks. The trial was found to be feasible and acceptable for weight loss in this population. The controls, WW plus and WW group showed median (IQR) weight change of 0.07 (-0.4, 0.7) kg (p= 0.666), -2.90 (-6.5, -2.2) kg (p= 0.002) and -5.90 (-6.6, -5.1) kg (p= 0.001) respectively (between groups, p = 0.001). The regression model suggested that compared to participants in WW plus, participants in WW group lost significantly more weight (2.6 kg; 95% CI -0.38, -4.86) and control group participants lost significantly less weight (3.8 kg; 95% CI, 1.47, 6.16) over the 12 weeks. There were a number of significant improvements in different QoL scores in the intervention groups at 12 weeks. However, a significant difference in median (IQR) scores of the breast cancer specific QoL scale was observed between the three groups (p= 0.017) and it was higher in WW group [5.0 (1.5, 7.5)] compared to WW plus group [3.7 (2.0, 4.5)] and control [0.5 (-2.0, 2.2)]. Conclusions: The outcomes of this theoretically informed trial suggest that providing WW vouchers for overweight and obese women treated for breast cancer is feasible and shows promise for weight loss and improved QoL.