La douleur est une expérience subjective multidimensionnelle pouvant être modulée par plusieurs facteurs cognitifs. L’impact des attentes liées à une expérience douloureuse imminente a été largement étudié dans un contexte d’analgésie placebo et il a été suggéré que la présence d’attentes conscientes de soulagement est nécessaire à la production d’une réduction de douleur. Par ailleurs, certaines études cliniques ont observé une amélioration thérapeutique après l’administration d’un placebo, même lors du sommeil, ce qui suggère qu’un effet placebo peut être rencontré même en absence d’attentes explicites de soulagement. La première étude de cette thèse vise donc à examiner si une réduction de douleur, ainsi qu’une diminution des perturbations du sommeil associées à des stimulations nociceptives expérimentales, peuvent être rencontrées suite à l’induction d’attentes de soulagement nocturne. Les résultats démontrent qu’une réduction de douleur et des perturbations du sommeil a effectivement été rapportée rétrospectivement suite à l’application d’un placebo, De plus, le traitement placebo semble moduler la réactivité à la douleur expérimentale durant le sommeil, en fonction des stades de sommeil dans lesquelles les stimulations sont présentées. Bien que le développement d’une analgésie placebo repose sur la génération d’attentes de soulagement, il semble que l’exposition préalable à un traitement efficace augmente l’ampleur de l’effet, ce qui suggère que des phénomènes d’apprentissage associatif puissent également être impliqués dans la genèse de ces effets. Comme un rôle du sommeil à été montré dans l’apprentissage et la mémorisation de plusieurs aptitudes, l’objectif de la seconde étude était d’examiner la possibilité que la présence d’un épisode de sommeil entre l’induction et l’évaluation d’un effet placebo puisse renforcer l’intégration des attentes et par conséquent, favoriser la production d’effets dépendants des attentes. Les résultats ont effectivement montré que le sommeil augmente l’association entre les attentes et le soulagement, et que celles-ci semblent liées à la durée relative de sommeil REM mesurée suite à l’induction. Dans l’ensemble cette thèse démontre que le sommeil peut influencer la production d’une analgésie placebo, et ce, à plusieurs niveaux. / Pain is a multidimensional experience which can be modulated by many cognitive factors. The impact of expectations associated with an impending painful experience was largely studied in the context of placebo analgesia, and it was suggested that the presence of conscious relief expectation was necessary for the production of pain reduction. On the other hand, some clinical studies have observed therapeutic improvements following the administration of a placebo, even during sleep, which suggest that a placebo effect can be seen even in the absence of explicit relief expectation. The first study of this thesis aims at examining if a pain reduction, as well as a decrease in sleep disturbances associated with the experimental pain stimuli, can be seen following the induction of night-time expectations. The results indeed showed a significant reduction in pain and associated sleep disturbances evaluated retrospectively following the application of a placebo. In addition, placebo treatment appears to modulate responses to experimental pain during sleep, in a manner dependent of the sleep stage in which they are presented. Although the development of placebo analgesia relies on the production of relief expectations, previous exposure to efficient treatment appears to augment the magnitude of the effect. This suggests that associative learning processes might also be implicated in the genesis of these effects. As a role of sleep was shown in the learning of different aptitudes, the objective of the second study was to examine whether the presence of a sleep episode between the placebo induction and the evaluation of the effect can reinforce the integration of expectations and consequently, favour the production of expectation-dependent effects. The results show that sleep increases the association between expectation and relief, and that the level of expectation appears to be linked to the relative duration of REM sleep measured after the induction. Globally, this thesis demonstrates that sleep can influence placebo analgesia at many levels.

Le neurofeedback (NF) suscite actuellement un vif intérêt dans la prise en charge du trouble déficitaire de l’attention avec hyperactivité (TDAH) chez l’enfant. Proposée comme méthode alternative à la médication par de nombreux cliniciens, notamment aux États-Unis, le NF est une intervention non-invasive de type électrophysiologique qui repose sur l’apprentissage par conditionnement opérant de l’autorégulation d’ondes cérébrales déviantes. Les études empiriques qui étayent cette pratique font toutefois l’objet de virulentes critiques de la part de spécialistes dans le domaine du TDAH en raison de résultats systématiquement positifs mais non spécifiques, auxquels s’ajoutent de nombreuses lacunes méthodologiques. Les travaux de cette thèse visent à appliquer une méthodologie stricte de type essai clinique contrôlé avec assignation aléatoire afin d’isoler les effets particuliers du NF, en appliquant un protocole d’entraînement propre au déficit primaire sous-tendant le TDAH, soit l’inhibition motrice, dans le but d’évaluer la spécificité de cette intervention. Dans un premier temps, les connaissances relatives à la nosologie du TDAH, à ses principaux traitements, au NF et aux capacités d’inhibition chez l’enfant ayant un TDAH sont présentées (Chapitre 1). Ensuite, les études réalisées dans le cadre de cette thèse sont exposées. Dans l’étude initiale, la spécificité du NF est évaluée sur les capacités d’inhibition grâce à des mesures subjectives, soit des questionnaires de comportements complétés par les parents, ainsi que des mesures objectives, à savoir des tâches neuropsychologiques (Chapitre 2). Afin de préciser davantage les conséquences d’un entraînement à l’autorégulation d’ondes cérébrales, l’étude subséquente s’est intéressée à l’impact neurophysiologiques de l’amélioration des capacités d’inhibition, par le biais d’une étude en potentiels évoqués employant une tâche de performance continue de type Stop-signal (Chapitre 3). Les principaux résultats reflètent un recrutement sous optimal, avec une puissance statistique insuffisante pour réaliser des statistiques quantitatives de groupe. Néanmoins, l’appréciation des données selon une approche d’étude de cas multiples permet de mettre en évidence la présence d’une réponse placebo sur les capacités d’inhibition suite à un entraînement en NF. Finalement, les implications de la taille de l’échantillon, ainsi que les limites et les critiques de ces études sont discutées au Chapitre 4. / In recent years, there has been a lively interest in the use of neurofeedback (NF) as an alternative treatment to pharmacotherapy in pediatric Attention-deficit hyperactivity disorder (ADHD). NF is defined as an operant conditioning procedure whereby an individual learns to self-regulate electrical brain activity. Yet, empirical studies supporting its practice are harshly criticized in the field of ADHD research due to systematic unspecific positive results associated to numerous methodological flaws. Studies presented in this dissertation aim at applying a randomized placebo-controlled clinical trial to the investigation of NF specific effects. In order to further establish treatment specificity, we trained the participants using a NF protocol characteristic to motor-inhibition functioning since it has repeatedly been described as the core deficit in ADHD. The fist part of this thesis comprises a brief review of knowledge concerning ADHD, principal treatments offered for this disorder, NF research in pediatric ADHD and inhibition abilities in these children (Chapter 1). Following are the two studies conducted as part of this dissertation. In the initial study, effects of NF training are investigated on inhibition capacities by means of behavior rating scales and neuropsychological tests (Chapter 2). With the aim of further defining the consequence of training to self-regulate ones brain activity, the subsequent study looks at the neurophysiologic impact of improving inhibition capacities with an event-related potential study using a Stop-signal continuous performance task (Chapter 3). The principal results reveal a non optimal recruitment, with insufficient statistical power, thus precluding quantitative group statistics. Nevertheless, appreciating the data from a multiple case study perspective enables to suggest that a placebo response could be at play following NF training, such as measured by improvements on inhibition capacities. Finally, the implications of such a small sample size, limits and critics of these studies are discussed in Chapter 4.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O tratamento para a Síndrome da Apnéia Obstrutiva do Sono (SAOS) mostra-se necessário devido às co-morbidades associadas ao quadro da síndrome. Fatores como problemas cardiovasculares, e aumento das chances de acidentes automobilísticos e de trabalho, além da diminuição da qualidade de vida, fazem dessa condição um sério problema a ser tratado. Dentre os tratamentos clínicos têm recebido especial atenção os aparelhos intra-orais por se tratar de um método simples e não invasivo. Os objetivos deste trabalho foram avaliar através dos índices polissinográficos as melhoras produzidas por um aparelho experimental e um aparelho placebo, e através de radiografias cefalométricas analisar fatores anatômicos relacionados com a severidade inicial do quadro e com as alterações do quadro da síndrome decorrentes do uso do aparelho experimental (Twin Block). Dezenove pacientes participaram deste estudo que foi prospectivo, com acompanhamento médio de 10,5 meses, cruzado, randomizado e duplo-cego. Foram feitas polissonografias iniciais e em uso dos aparelhos, após em média 6,47 (d.p.=2,01) meses do uso do Twin Block e 3,8 (d.p.=0,84) meses do uso do placebo e radiografias cefalométricas inicial e com o aparelho Twin Block em posição. Os dados pareados foram avaliados pelo teste de Wilcoxon, os não pareados pelos testes t de Student e Mann-Whitney e a comparação de proporções com o teste z, todos com 5% de significância (p<0.05). Os resultados mostraram tendências, embora não comprovadas estatisticamente, nas quais o grupo com SAOS moderada apresentou medidas de faringe menores e posição do osso hióide menos caudal quando comparados com o grupo com SAOS leve; que houve melhor resposta à terapia com o Twin-Block do que com o placebo, considerando-se o índice de apnéias mais hipopnéias por hora de sono (IAH), o índice de apnéias por hora de sono (IA), e a percentagem de sono REM; que a posição do osso hióide vertical diminuiu mais nos pacientes que melhoraram, tanto para o IAH quanto para o IA, que a maioria das medidas de faringe sofreram maior aumento nos pacientes que melhoraram em comparação com os que não melhoraram.Também foi possível estabelecer-se correlação positiva entre hipofaringe (HF) e os pacientes que melhoraram (avaliando pelo IAH), entre distância do osso hióide a terceira vértebra cervical (DHTV), faringe na altura do plano oclusal [NF(2)], largura do palato mole (PM) e os pacientes que melhoraram (avaliando pelo IA), além de entre NF (2) e os pacientes que não melhoraram (avaliando pelo IA). Conclui-se que o Twin Block mostrou-se clinicamente mais efetivo que o aparelho placebo no controle da SAOS, que algumas medições cefalométricas podem estar relacionadas com a severidade da síndrome medida inicialmente e que há variações de alterações anatômicas entre os pacientes que responderam e não responderam à terapia com aparelho intra-oral. / The treatment for the Obstructive Sleep Apnea Syndrome (OSAS) is necessary due to the co-morbidities associated with the syndrome. Factors such as cardiovascular problems, higher risk of automobile and work accidents, in addition to the decreased quality of life, makes the condition a serious problem to be treated. Among the treatments, clinicians have given special attention to the intra-oral appliances because it is simple and noninvasive. The objectives of this study were to evaluate by polysomnographyc indexes the improvements produced by both experimental and placebo units, and by cephalometric radiographs examine anatomical factors related with the initial severity of the syndrome and with the changes resulting from the use of the experimental appliance (Twin Block). Nineteen patients participated in this crossover, randomized, double-blind and prospective study, with monitoring average of 10.5 months. Polysomnographys were made in the initial use of the devices, after an average of 6.47 months (s.d. = 2.01) of Twin Block use and 3.8 months (s.d. = 0.84) of placebo use, along with cephalometric radiographs taken initially and with the Twin Block in position. Paired data were analyzed by the Wilcoxon test, non-paired by the Student t test and Mann-Whitney and compared proportions with the test z, all with 5% of significance (p <0.05). The results showed trends, though not statistically proven, that the group with moderate OSAS presented lower measures for the pharynx and higher hyoid bone position when compared to the group with mild OSAS; that the patients were more responsive to therapy with Twin-Block than with placebo, considering the index of more apnea hypopnea per hour of sleep (AHI), the index of sleep apnea per hour (AI), and the percentage of REM sleep; that the position of the vertical hyoid bone decreased more in patients who improved, both for the AHI and for the AI; that most pharyngeal measures suffered greater increase in patients who improved in comparison with those who did not get better. It could also be established a positive correlation between hypopharynx (HF) and patients who improved (by assessing AHI), distance between the hyoid bone and the third cervical vertebra (DHTV), pharynx in the occlusal plain [NF (2)], the width of the soft palate (PM) and patients that improved (by assessing AI), and between NF (2) and patients who had not improved (by assessing AI). It is concluded that the Twin Block was clinically more effective than the placebo unit in the control of OSAS, that some cephalometric measurements may be related to the severity of the syndrome measure initially and that there are variations in anatomic changes among patients who responded and not responded to therapy with intra-oral device.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O tratamento para a Síndrome da Apnéia Obstrutiva do Sono (SAOS) mostra-se necessário devido às co-morbidades associadas ao quadro da síndrome. Fatores como problemas cardiovasculares, e aumento das chances de acidentes automobilísticos e de trabalho, além da diminuição da qualidade de vida, fazem dessa condição um sério problema a ser tratado. Dentre os tratamentos clínicos têm recebido especial atenção os aparelhos intra-orais por se tratar de um método simples e não invasivo. Os objetivos deste trabalho foram avaliar através dos índices polissinográficos as melhoras produzidas por um aparelho experimental e um aparelho placebo, e através de radiografias cefalométricas analisar fatores anatômicos relacionados com a severidade inicial do quadro e com as alterações do quadro da síndrome decorrentes do uso do aparelho experimental (Twin Block). Dezenove pacientes participaram deste estudo que foi prospectivo, com acompanhamento médio de 10,5 meses, cruzado, randomizado e duplo-cego. Foram feitas polissonografias iniciais e em uso dos aparelhos, após em média 6,47 (d.p.=2,01) meses do uso do Twin Block e 3,8 (d.p.=0,84) meses do uso do placebo e radiografias cefalométricas inicial e com o aparelho Twin Block em posição. Os dados pareados foram avaliados pelo teste de Wilcoxon, os não pareados pelos testes t de Student e Mann-Whitney e a comparação de proporções com o teste z, todos com 5% de significância (p<0.05). Os resultados mostraram tendências, embora não comprovadas estatisticamente, nas quais o grupo com SAOS moderada apresentou medidas de faringe menores e posição do osso hióide menos caudal quando comparados com o grupo com SAOS leve; que houve melhor resposta à terapia com o Twin-Block do que com o placebo, considerando-se o índice de apnéias mais hipopnéias por hora de sono (IAH), o índice de apnéias por hora de sono (IA), e a percentagem de sono REM; que a posição do osso hióide vertical diminuiu mais nos pacientes que melhoraram, tanto para o IAH quanto para o IA, que a maioria das medidas de faringe sofreram maior aumento nos pacientes que melhoraram em comparação com os que não melhoraram.Também foi possível estabelecer-se correlação positiva entre hipofaringe (HF) e os pacientes que melhoraram (avaliando pelo IAH), entre distância do osso hióide a terceira vértebra cervical (DHTV), faringe na altura do plano oclusal [NF(2)], largura do palato mole (PM) e os pacientes que melhoraram (avaliando pelo IA), além de entre NF (2) e os pacientes que não melhoraram (avaliando pelo IA). Conclui-se que o Twin Block mostrou-se clinicamente mais efetivo que o aparelho placebo no controle da SAOS, que algumas medições cefalométricas podem estar relacionadas com a severidade da síndrome medida inicialmente e que há variações de alterações anatômicas entre os pacientes que responderam e não responderam à terapia com aparelho intra-oral. / The treatment for the Obstructive Sleep Apnea Syndrome (OSAS) is necessary due to the co-morbidities associated with the syndrome. Factors such as cardiovascular problems, higher risk of automobile and work accidents, in addition to the decreased quality of life, makes the condition a serious problem to be treated. Among the treatments, clinicians have given special attention to the intra-oral appliances because it is simple and noninvasive. The objectives of this study were to evaluate by polysomnographyc indexes the improvements produced by both experimental and placebo units, and by cephalometric radiographs examine anatomical factors related with the initial severity of the syndrome and with the changes resulting from the use of the experimental appliance (Twin Block). Nineteen patients participated in this crossover, randomized, double-blind and prospective study, with monitoring average of 10.5 months. Polysomnographys were made in the initial use of the devices, after an average of 6.47 months (s.d. = 2.01) of Twin Block use and 3.8 months (s.d. = 0.84) of placebo use, along with cephalometric radiographs taken initially and with the Twin Block in position. Paired data were analyzed by the Wilcoxon test, non-paired by the Student t test and Mann-Whitney and compared proportions with the test z, all with 5% of significance (p <0.05). The results showed trends, though not statistically proven, that the group with moderate OSAS presented lower measures for the pharynx and higher hyoid bone position when compared to the group with mild OSAS; that the patients were more responsive to therapy with Twin-Block than with placebo, considering the index of more apnea hypopnea per hour of sleep (AHI), the index of sleep apnea per hour (AI), and the percentage of REM sleep; that the position of the vertical hyoid bone decreased more in patients who improved, both for the AHI and for the AI; that most pharyngeal measures suffered greater increase in patients who improved in comparison with those who did not get better. It could also be established a positive correlation between hypopharynx (HF) and patients who improved (by assessing AHI), distance between the hyoid bone and the third cervical vertebra (DHTV), pharynx in the occlusal plain [NF (2)], the width of the soft palate (PM) and patients that improved (by assessing AI), and between NF (2) and patients who had not improved (by assessing AI). It is concluded that the Twin Block was clinically more effective than the placebo unit in the control of OSAS, that some cephalometric measurements may be related to the severity of the syndrome measure initially and that there are variations in anatomic changes among patients who responded and not responded to therapy with intra-oral device.

O jogo patológico é classificado como um transtorno do controle dos impulsos, que envolve a fissura e a impulsividade para jogar, causando prejuízos sociais. Estudos prévios sugeriram que o topiramato poderia ser mais eficaz do que o placebo no tratamento de alguns transtornos relacionados com impulsividade, tais como transtorno de compulsão alimentar periódico, alcoolismo e dependência de cocaína. O principal objetivo deste estudo foi verificar se o topiramato foi superior ao placebo em controlar fissura e reduzir pensamentos e comportamentos relacionados ao jogo. Método: os jogadores patológicos foram aleatoriamente distribuídos em um de dois grupos: o que recebeu topiramato (n=15) e o que recebeu placebo (n=15) por 12 semanas. Durante o estudo, todos os pacientes participaram de quatro sessões psicoeducacionais, baseadas no programa de 12 passos dos jogadores anônimos. A principal variável de desfecho foi a escala G-SAS. As demais variáveis de desfecho foram consideradas secuindárias, sendo as escalas/entrevista: Escala Yale Brown de obsessão e compulsão adaptada para jogo patológico (PG-YBOCS), Timeline Follow-Back (TFB), questionário de crença de jogadores (GBQ), escala de impulsividade de Barratt (BIS-11), escala de impressão clínica global (CGI), escala de adequação social (EAS). Nos resultados, os pacientes que receberam topiramato obtiveram melhora nos escores das escalas: G-SAS, o que implica em redução dos sintomas de fissura e abstinência; PG-YBOCS, que mostrou redução de comportamentos e obsessões relacionados ao jogo; GBQ, que demonstrou redução de crenças supersticiosas e melhora cognitiva e EAS, que mostrou melhora na qualidade de vida. A entrevista TFB mostrou maiores reduções na média de tempo e quantia de dinheiro gasto em jogo no grupo topiramato em relação ao grupo placebo. Conclusão: o uso de topiramato associado a quatro sessões psicoeducacionais foi superior ao uso de placebo associado a quatro sessões psicoeducacionais, na redução de fissura, freqüência, comportamentos, superstições, quantidade de tempo e dinheiro destinados ao jogo, com melhora na qualidade de vida / Pathological gambling is an impulse control disorder that involves craving and impulsivity to gamble and in which gambling thoughts and behaviors may cause social impairment. Previous studies suggested that topiramate could be effective in the treatment of some disorders related to impulsivity, such as binge eating disorder, alcoholism or cocaine addiction. The studys main goal was to verify if topiramate was superior to placebo in controlling craving and reducing thoughts and behaviors related to gambling. Methods: pathological gamblers were randomized to topiramate (n=15) or placebo (n=15) in a 12-week, double-blind placebo controlled trial. During the 12 weeks the patients had four sessions of a program based on the 12 steps of Anonymous Gamblers. The primary outcome measure was the Gambling Symptom Assessment Scale (G-SAS), which evaluates symptoms related to abstinence. As secondary outcome measures it was used the following scales or interviews: Yale Brown Obsessive Compulsive Scale adapted for Pathological Gambling (PG-YBOCS), Timeline Follow-Back Method (TFB), Gamblers Beliefs Questionnaire (GBQ), Barratt Impulsiveness Scale (BIS-11), Clinical Global Impression (CGI), Social Adjustment Scale (SAS). Results: There were statistic robust findings in some of the scales used in this study. The group of patients who took topiramate had improvement in the scores of the G-SAS, which implies reduction in the symptoms of craving and abstinence; PG-YBOCS, which showed reductions in the behaviors and obsessions related to gambling; GBG, which revealed reduction of superstitious thoughts and cognitive improvement, and EAS that showed improvement in the quality of life. TFB showed that the topiramate group had more reductions in the average of time and money spent on gambling than the placebo group. Conclusions: According to the results, topiramate associated with four sessions based in cognitive restructuring were superior to placebo associated with four sessions based in cognitive restructuring in reducing craving, frequency, behaviors and superstitions related to gambling, and amount of time and money used in gambling. Moreover, according to SAS, the group that took topiramate had better improvement in the quality of life than the placebo group

Hintergrund:Allergische Rhinitis führt zu nasaler Hyperreagibilität mit den Symptomen Obstruktion, Sekretion und Niesreiz. Diese wiederkehrenden Symptome haben einen störenden Einfluss auf die Lebensqualität der Betroffenden mit negativen Auswirkungen auf ihre Leistungsfähigkeit, Arbeitsproduktivität und ihr Sozialleben. Zudem kommt es dadurch zu hohen Kosten im Gesundheitswesen.Ziel dieser monozentrischen, randomisierten, doppelblinden, Placebo-kontrollierten, dreiarmigen Studie der Phase II, die an 33 Personen mit allergischer oder intrinsischer Rhinitis durchgeführt wurde, war die Bestimmung der therapeutischen Wirksamkeit von nasal mit einem Merocel®-Schwämmchen appliziertem Xeomin® (BoNTA) auf die nasale Hypersekretion der Patienten. Methode:Es wurde nach drei Gruppen unterteilt: Die erste Gruppe erhielt 80 Einheiten BoNTA pro Nasenloch in einen Schwamm in der Nase. Die zweite die Hälfte der Dosis und die dritte nur Placebo (Kochsalzlösung). Während eines sich anschließenden sechsmonatigen Beobachtungszeitraums wurden die Patienten regelmäßig untersucht.Als primäre Zielgröße wurde die Menge des nasalen Sekretflusses nach BoNTA- oder Placebo-Gabe definiert. Diese wurde durch das Zählen des vom Patienten im Nasentagebuch dokumentierten Papiertaschentücherverbrauchs bestimmt. Die Patienten benutzten hierzu jedes Taschentuch nur einmalig. Eine sekundäre Zielgröße war die Gewichtsveränderung der Sekretmenge in den Taschentüchern, die am Tag vor der Kontrollvisite in einer verschließbaren Plastiktüte gesammelt wurden.Als weitere Zielgrößen wurden die Veränderung der Nasenatmungsbehinderung, des nasalen Juckreizes, des Niesreizes, des Geruchssinnes und unerwünschte Nebenwirkungen wie Trockenheit der Nasenschleimhaut oder Epistaxis dokumentiert. Auch wurde eine Rhinomanometrie und Olfaktometrie bei den Kontrollvisiten durchgeführt.Ergebnis:Die Analysen der Daten des Taschentuchzählens (primäre Zielgröße) ergab im Vergleich zwischen der höheren und niedrigeren Xeomin®-Dosisgruppe und der Placebo-Gruppe keinen signifikanten Unterschied (p=0,2203/ p=0,8469). Der Verlauf der Änderung des Sekretflusses unter Xeomin® im Vergleich zum Placebo war über die Zeit nicht unterschiedlich. Es zeigte sich lediglich, dass eine Tendenz der Verminderung des Taschentuchverbrauchs in allen Gruppen bestand. Das bedeutet, dass keine eindeutige Wirkung auf die nasale Schleimhaut durch Xeomin® feststellbar war.Demgegenüber stehen die Ergebnisse aus der Analyse des Auswiegens der Taschentücher (sekundäre Zielgröße). Entgegen dem Kriterium „Veränderung der Anzahl der verbrauchten Taschentücher“ ergab sich über das Auswiegen der nasalen Sekretmenge, dass im Vergleich zwischen der Gruppe mit der höheren Xeomin®-Dosis und der mit Placebo behandelten ein signifikanter Unterschied bezüglich der Sekretmenge (p=0,0064) bestand.Es scheint die objektivere Messung des Gewichtes für zukünftige Untersuchungen geeigneter zu sein.Die Vergleiche zwischen den Gruppen erbrachten keine deutlichen Hinweise auf einen Behandlungseffekt durch BoNTA bezüglich der Nasenatmungsbehinderung, des nasalen Juckreizes, des Niesreizes und des Geruchssinnes.Aufgrund der nur sehr geringen Nebenwirkungen handelt es sich um eine risikoarme Behandlungsmethode. Die Verlaufsdaten zur Rhinomanometrie und Olfaktometrie blieben in allen Gruppen auf einem vergleichbaren Niveau, sodass sich hieraus keine Unterschiede zwischen den Gruppen ergaben.

Reduction of long-term mortality risk, an important clinical outcome for people in alcohol dependence treatment, can rarely be established in randomized controlled trials (RCTs). We calculated the reduction in all-cause mortality risk using data from short-term (6 and 12 months) double-blind RCTs comparing as-needed nalmefene treatment to placebo, and mortality risks from meta-analyses on all-cause-mortality risk by reduction of drinking in people with alcohol dependence. A reduction in drinking in the RCTs was defined by shifts in drinking risk levels established by the European Medicines Agency. Results showed that the reduction of drinking in the nalmefene group was associated with a reduction in mortality risk by 8% (95% CI: 2%, 13%) when compared to the placebo group. Sensitivity analyses confirmed a significant effect. Thus comparing the difference between nalmefene and placebo in reduction in drinking levels with results on all-cause mortality risk from meta-analyses indicated a clinically relevant reduction in mortality risk. Given the high mortality risk of people with alcohol dependence, abstinence or a reduction in drinking have been shown to reduce mortality risk and should be considered treatment goals.

Magister Scientiae Dentium - MSc(Dent) / Background and aim: Managing orthodontic pain traditionally involves the prescription of non-steroidal anti-inflammatory drugs combined with other analgesic medication. Sugar-free chewing gum has been advocated in the control of orthodontic pain due to its mechanical and physiological effects on periodontal tissue; however, the literature is scant. The ‘placebo effect’ that conventional sugar-free chewing gum may have in the relief of orthodontic pain has not been documented. The aim of this study was to compare the effectiveness of conventional sugar-free chewing gum in reducing orthodontic pain associated with fixed appliances with a placebo (sugar-free sweets) medicament. Objectives: The objectives of the study were to determine if there were differences in pain reporting between the sugar-free chewing gum and the placebo, to ascertain whether gender influenced pain scores and to observe any differences in pain reporting between different orthodontic techniques.

The environmental concern has become a well discussed topic within today’s society and as a result awareness of the impact human behaviour has on the environment is continuously increasing. This concern is something companies take advantage of when marketing, as for instance by promoting their products or services as eco-labelled. Eco-labelled products have further shown to involve a lot of consumer opinions, and are thus common to study in relation to consumer attitudes. Theories also show that eco-labelled goods have been idealised in favour of conventional ones, referred to as a marketing placebo effect. In connection to this, companies have started to point interest at eco-labelled technology, which has become a recent phenomenon attracting attention. Nonetheless, the existing theory regarding this phenomenon has been mainly applied on specific areas, such as the food industry. The purpose of this study was therefore to explain the marketing placebo effect on eco-labelled technology. 162 experiments were conducted using one experiment group and one control group, in order to be able to detect an eventual marketing placebo effect when implementing an eco-label, using attitudes as an influencer. Based on the results, it was revealed that attitudes are crucial to take into consideration when applying an eco-label in a technology context. This as it was concluded that attitudes act as a trigger evoking a marketing placebo effect. The findings from this study contradicts current theories on how different factors cooperate in the process of a marketing placebo effect, and advances has thus been made in how the marketing placebo effect works when applied in a technology context.

This thesis is about the relationship between human bodies and instrumental technologies that can be use to measure them. It adopts the position that instruments are technological structures that evoke and manifest particular phenomena of embodied life. However, through their history of association and use in the sciences and scientific medicine, instruments tend to be attached to a particular ontology, that of mechanical objectivity. Embarking from research into the artistic uses of physiological sensor technology in creative practices such as performance and installation art, this thesis asks whether it is possible to use instruments in a way that departs from their association with scientific objectivity. Drawing on philosophers who have developed an understanding of the relationship of instrumental technologies and human bodies as co-constructive, it explores how this model of con-construction might be understood to offer an alternative ontology for understanding the use of instruments in practices outside of science and scientific medicine. The project is therefore suggestive of degrees of freedom and flexibility that are open to exploitation by creative practices in the realm of instrumentation as an alternative to orthodox rationalisations of the value of scientific equipment as authentic, revealing and objective. The major contribution of the thesis is that transfers and synthesises arguments and evidence from the history and philosophy of sciences that serve to demonstrate how the instrumental measurement of human bodies can be considered to be a form of creative practice. It assembles a position based on the work of thinkers from a number of disciplines, particularly philosophy of science, technology, and the medical humanities. These offer examples of ontological frameworks within which the difference between the realm of the instrumental, material, biological, and the objective, and the phenomenal, meaningful and subjective, might be collapsed. Doing this, the thesis sheds light on how physical devices might enter into the interplay of making, mattering and objectifying the immaterial, a realm that it might be considered the role of artists to manifest. Drawing on contemporary, and secondary, accounts of the development of empirical testing in the medical sciences, the thesis agues for the recovery of a romantic account of human physiology, in which the imagination and meaning are active and embodied. It therefore offers to link the bodily and the instrumental through an extended-materialist account in which the physiological, rather than the psychological, is central. Developing a response to constructionist models of the body and instrumentation, the thesis concludes that a model of the poetic may be adopted as a method for understanding the opportunities and imperatives inherent in the avoidance of deterministic approaches to biosignalling technologies. In doing this, the thesis contributes particularly to the creative arts and technology research practices concerned with the use of body sensor technologies in humanistic applications. It complements the existing works by artists in this area that make use of instruments by assembling a number of theoretical readings and interpretations of how instruments work – among them the thermometer, lie detector, and automatograph – which illustrate the argument that that is possible to operate from a theoretical position within which instruments are both material, performative and symbolic.