En psykossjukdom har en person när verklighetsuppfattningen av andra människor och världen förändras. Patienter som har en psykossjukdom upplever att de lider på grund av sin sjukdom och upplever sig ha funktionshinder och sämre livskvalitet än andra människor i samhället. Dessa personer behöver därför erbjudas insatser från hälso- och sjukvården. Tidigare forskning visar att personer med psykossjukdomar upplever stigmatisering både ute i samhället och i vården. Patienterna känner sig inte tillräckligt delaktiga i sin vård och det finns en brist i relationen mellan patient och sjuksköterska. Syftet med denna litteraturstudie är att belysa patienters upplevelse och erfarenheter av den psykiatriska vården. Studien är en kvalitativ litteraturstudie och dataanalys genomfördes med en litteraturöversikt. Resultatet i litteraturstudien kan beskrivas utifrån tre olika teman med tillhörande subkategorier. I studien diskuteras relationen mellan patient och sjuksköterska: t.ex. kontroll och självbestämmande hos patienten och bemötandet av sjuksköterskorna. Det diskuteras också om hur förtroende och trygghet för patienten bidrar till ökat välbefinnande och minskat lidande.  Litteraturstudiens slutsats är att sjuksköterskor har en viktig roll och påverkan i hur patienten upplever vården. Maktfördelningen och samspelet mellan personal och patient bör vara dynamisk så ofta som möjligt och beroende på omständigheter skifta. Den psykiatriska vården bör fokusera mer på relationen och samarbetet mellan personal. / Psychosis is when one’s experience of the world and other people is changed. Patients with psychosis report that they suffer because of their illness, have a lower quality of life, and that psychosis is a form of disability. These people therefore need help from the healthcare system. Early research shows that people with different psychotic illnesses experience stigma in society and in health care. Patients often do not feel included enough in their care and that there is something lacking in the relationship between patients and nurses. This literary study focuses on the patient experience of psychiatric care. Our analysis is broken into three main themes with subthemes. The study discusses the relationship between patients and nurses such as, “control and autonomy of the patient and the treatment from nurses.” It also discusses how the experience of trust, security and safety of the patient can affect well-being and lessen suffering. Through this analysis, we found that nurses have an important role in how a patient experiences care. Power dynamics and the interaction between patient and nurse should adapt depending on the circumstances and how they change. Psychiatric care should focus on the relationship and interaction between personnel and patients.

Pump and treat remediation is the most commonly used method to remediate contaminated aquifers, but the effectiveness decreases when heterogeneities are introduced. Fractures within the matrix cause large differences in hydraulic conductivity. The low hydraulic conductivity of the matrix acts as an area of storage for contaminant, allowing for attenuation of the plume. The attenuation of the plume causes the effectiveness of the system to decrease and cost of remediation to increase. In order to understand what parameters enhance contaminant storage in the matrix, rapid transport in fractures, and both of their influences on the efficiency of the pumping system, a hypothetical model was developed to simulate the release and remediation of a plume using pumping. The code used was HydroGeoSphere, which allowed for the interpretation of parameters influencing contaminant storage during the withdrawal phase of the pump and treat remediation by allowing transport of contaminant within both the matrix and the fractures. Matrix parameters of porosity and hydraulic conductivity influenced the effectiveness of the withdrawal system most. For instance, the difference in percent mass extracted between porosity values of 0.01 and 0.4 was 23.75%, while the difference between fracture lengths of 200 and 400 m was 5.59%. Fracture pattern influenced where the stored contaminant was located within the matrix. Downgradient of the source, six different fracture patterns resulted in a difference in relative concentration of 0.4 at the start of the withdrawal phase. Evaluation of remediation included both percent extraction of contaminant and finer scale remediation of the contaminant specifically within the matrix. Multiple length-scale observations helped determine how fracture and matrix parameters influence remediation in dual permeability media. / Geology

本研究之目的，在於：探討非指導式團體遊戲治療對學前兒童社會關係及社會能力之 影響效果。 本研究以台北市私立中山小學附設幼稚園之幼兒為對象，隨機抽取其中七班幼兒，再 選取其中社會能力及社會關係較差之幼兒四十八名為樣本。採不相等控制組前後測設 計。實驗組接受為期六週共十次之非指導式團體遊戲治療，控制組則不參加。 本研究之假設有二： （一）非指導式團體遊戲治療對學前兒童之社會能力有顯著效果。 （二）非指導式團體遊戲治療對學前兒童之社會關係有顯著效果。 （三）不同性別之學前兒童接受團體遊戲治療後，其社會能力及社會關係將有顯著差 異。 （四）不同年級之學前兒童接受團體遊戲治療後，其社會能力及社會關係將有顯著差 異。 本研究之工具計有（一）加州學前兒童社會能力量表。（二）照片式社會計量法。 本研究之統計方法採獨立樣本二因子共變數分析法，以前測為共變數，後測分數為變 數，以考驗兩組幼兒在處理、性別與年級之間的效果。 本研究結果發現：假設獲得部份支持。 一、實驗組與控制組幼兒在社會能大部分之「動作能力」上，具有立即性效果。 二、實驗組與控制組幼兒在社會能力部分之「主動性」上具有立即性效果。 三、實驗組與控制組幼兒在社會關係上具有立即性效果。

MSc dissertation - Faculty of Engineering and the Built Environment / Waste electrolyte from fluorine cells is a major waste problem for the fluorine chemical industry. Processes have to be developed to reduce, recycle and re-use the spent electrolyte that has up to now been stockpiled. This dissertation is a compilation of the research work that has been done to derive a process to treat waste electrolyte for re-use. Different conversion processes were investigated to develop a Waste Management plan for the fluorine generating facility in respect of the electrolyte. Gravity settling, centrifuging, filtration, the addition of KF.HF to the to the electrolyte to decrease the HF concentration in the electrolyte and consequently decrease the solubility of Fe, Cu and Ni and addition of NaOH to the electrolyte to convert soluble Fe to the insoluble triple salt were tested. Gravity settling and centrifuging were shown to produce the best solution. However, significant sedimentation of the insoluble metal impurities in the electrolyte is timeously. The implementation of sedimentation as an industrial separation process to purify waste electrolyte of excess metal impurities is therefore impractical. The results indicated that sparging molten electrolyte with N2 gas to remove HF (thus precipitating soluble Fe, Cu and Ni, and removing moisture to reduce corrosion of metal components), followed by sediment centrifuging, appears to be a practical basis for an industrial waste electrolyte treatment process. During an assessment carried out by the Economics Trends Research Group (ETRG) (3) at the University of Cape Town a strong argument was made for the need to direct companies in South Africa to address environmental concerns with high priority. In South Africa there is very little awareness of the concept of Clean Technology. Not only must the level of contamination be reduced before waste is released into the environment, but natural resources like water must be conserved, and energy consumption must be reduced. Public concern over degradation of the environment can no longer be ignored. Globally, the chemical industries are considered to be the main culprits in the degradation of the environment. The assessment carried out by the ETRG showed that the chemical industries are classed among the top 5 generators of toxic and hazardous waste in every country. The metallurgical sector (mining) is in most cases classed as the top waste generator. Development and implementation of technologies that are more efficient are not a matter of choice any more. Each new facility that is developed should meet the challenge of generating as little waste as possible. Unfortunately, many old industries and facilities did not focus on increasing efficiency and minimising waste. These old facilities experience a challenge now to develop technology to make them part of this Cleaner Production and Technology era. Cleaner Production implies generating less effluent or waste and recycling waste to be used as raw material in the same or another facility. Cleaner Production also concentrates on the increase of efficiency but this is often limited by the chemical properties of substances. This research was based on the ideas for implementation of Cleaner Production in the fluorine generation facility at Necsa. Waste reduction almost always implies investment in equipment and development of new technologies. However there is ample evidence to show that the cost of rehabilitation of contaminated environment is exceedingly high in comparison with the precautionary steps taken to prevent contamination. Waste/Effluent Management have become new buzz words in the industrial environment.

INTRODUÇÃO: A asma grave acomete menos de 10% dos asmáticos, mas tem um impacto desproporcional sobre a utilização de recursos de saúde, contribuindo para, pelo menos, metade dos custos diretos e indiretos da doença. A proporção de indivíduos obesos ou com sobrepeso é elevada em pacientes com asma grave. Na verdade, a obesidade é um fator de risco para a asma, está associada com a gravidade da doença, com pior resposta a corticosteroides e pior controle clínico. Estudos sobre os efeitos da perda de peso em pacientes com asma ainda são escassos. OBJETIVOS: Avaliar o impacto da perda de peso com medidas clínicas em pacientes com asma grave e obesidade. MÉTODOS: Este é um estudo prospectivo randomizado aberto com dois grupos paralelos. Os participantes eram obesos e com asma grave e que, depois de um período de run-in de três meses, não estavam controlados de acordo com critérios da GINA. Os pacientes elegíveis foram randomizados em uma proporção de 2:1 (perda de peso: controle). Todos os participantes passaram por consultas bimensais no ambulatório de asma e foram acompanhados por seis meses. O desfecho primário foi o nível de controle da asma seis meses após o início do programa de redução de peso medido pelo Questionário de Controle da Asma (ACQ). Os desfechos secundários incluíram o Teste de Controle da Asma (ACT), resultados de função pulmonar, o Questionário Respiratório de St. George (SGRQ), a mudança na reatividade brônquica à metacolina, o uso diário de medicação de alívio para asma, percentagem de dias livres de sintomas, número de visitas ao pronto-socorro e exacerbações, marcadores de inflamação das vias aéreas medidos pelo escarro induzido e pelo óxido nítrico exalado (FeNO). IgE, proteína C reactiva, eotaxina, leptina e Transforming Growth Factor beta 1 (TGF 1) também foram medidos. RESULTADOS: Trinta e três foram randomizados. O grupo era composto predominantemente de mulheres com obstrução moderada, aprisionamento de ar, aumento da resistência das vias aéreas e marcada eosinofilia no escarro. O aumento dos níveis séricos de IgE foram consistentes com uma predominância de asma atópica. Dos 22 pacientes randomizados para submeterem-se a tratamento para a obesidade, 12 atingiram a meta de perda de peso de, pelo menos, 10% do peso corporal. A redução de peso no grupo de tratamento foi associada com melhor controle da asma medido pelo ACQ, ACT e SGRQ. Houve aumento de dias sem sintomas, menor uso de medicação de resgate e menos visitas ao serviço de emergência durante o período de estudo. Não houve diferença no número de exacerbações. A capacidade vital forçada (CVF) aumentou significativamente no grupo de tratamento e permaneceu inalterada no grupo de controle. As outras medidas da função pulmonar não mostraram diferenças entre os grupos. A hiperreatividade das vias aéreas, níveis de óxido nítrico exalado e celularidade do escarro induzido não se alterou ao longo do estudo. Os níveis de leptina diminuíram em ambos os grupos. Os níveis séricos de IgE, proteína C-reactiva, eotaxina, e TGF-1 não se alteraram. CONCLUSÃO: Nosso estudo adiciona informações à controvérsia sobre o impacto da obesidade e seu tratamento no controle da asma. Nossos resultados sugerem que a redução de peso em pacientes obesos com asma grave melhore os resultados de asma por mecanismos não relacionados com a inflamação das vias aéreas e que o controle da asma pobre em pessoas obesas é, pelo menos em parte, o resultado de fatores relacionados com a obesidade. A abordagem terapêutica para pacientes obesos com dificuldade de tratar a asma deve ser destinada à redução de peso, bem como à intensificação do tratamento anti-inflamatório / INTRODUTION: Severe asthma affects less than 10% of asthmatics, but has a disproportionate impact on the use of health resources, contributing to at least half of the direct and indirect costs of the disease. The proportion of obese or overweight individuals is elevated in patients with severe asthma. In fact, obesity is a risk factor for asthma, is associated with the severity of the disease, a poor response to corticosteroids and worse clinical control. Studies on the effects of weight loss in patients with asthma are still scarce. OBJECTIVES: Assess the impact of weight loss with a medical weight loss program in patients with severe asthma associated with obesity. METHODS: This is a prospective open study with two randomized parallel groups. The participants were obese and with severe asthma and, after a three month run-in period, were not controlled according to GINA criteria. Eligible patients were randomized in a 2:1 ratio (weight loss:control). All participants attended bimonthly consultations in the asthma clinic and were followed for six months. The primary outcome measure was the level of asthma control 6 months after initiation of the weight reduction program quantified by using the Asthma Control Questionnaire (ACQ). Secondary clinical outcomes included the Asthma Control Test (ACT), lung function results, score on the St. Georges Respiratory Questionnaire (SGRQ), change in metacholine reactivity, daily use of asthma reliever medication, percentage of asthma symptom free days, number of visits to emergency room and exacerbations, markers of airway cellular inflammation measured in induced sputum and with exhaled nitric oxide (FeNO). IgE, C reactive protein, leptin, eotaxin and Transforming Growth Factor beta 1 (TGF1) levels in serum were also measured. RESULTS: Thirty-three patients were randomized. The group consisted predominantly of women with moderate airflow obstruction, air trapping, increased airway resistance and marked eosinophilia in the sputum. The increased serum levels of IgE were consistent with a predominance of atopic asthma. Of the 22 patients randomized to undergo treatment for obesity, 12 achieved the weight loss goal of at least 10% of body weight. The reduction in weight in the treatment group was associated with improvement in the control as measured by ACQ, ACT and SGRQ. There was increase of symptom-free days, less use of rescue medication and fewer visits to the emergency room during the study period. There were no differences in the number of exacerbations. The forced vital capacity (FVC) increased significantly in the treatment group and remained unchanged in the control group. The other measures of the pulmonary function showed no differences between groups. The airway hyperresponsiveness, exhaled nitric oxide levels and induced sputum cellularity did not change throughout the study. Leptin levels decreased in both groups. Serum levels of IgE, C-reactive protein, eotaxin, and TGF-1 did not change. CONCLUSION: Our study adds information to the controversy about the impact of obesity and its treatment on asthma control. Our results suggest that weight reduction in obese patients with severe asthma improves asthma outcomes by mechanisms not related to airway inflammation and that poor asthma control in people who are obese is at least in part the result of obesity-related factors. The therapeutic approach for obese patients with difficult-to-treat asthma should therefore be aimed at weight reduction as well as on intensifying antiinflammatory treatment

There is a great demand and need for oral health care during the course of HIV disease (HIV Costs and Services Utilization Study; Marcus et. al., 2005). HIV+ patients identified three key barriers to obtaining oral health treatment: 1) beliefs and attitudes of dental health care providers (DHCPs) may have lead to their unwillingness to treat HIV/AIDS patients; 2) the existence of racial and ethnic disparities in health care in the United States, and 3) how DHCPs perceive their risk of contracting HIV. The fear and stigma associated with treating patients with HIV further compromises their access to care and their health status. Oral health conditions associated with HIV disease are frequently more severe than those of the general population, making access to both dental and medical care imperative. Plus, Florida has some of the highest numbers of HIV/AIDS patients in the nation. This study was descriptive, cross-sectional and used quantitative methods to explore the dental hygienists' behavioral and normative beliefs, attitudes, and intentions toward treating patients with HIV/AIDS. A three-phase pilot study was conducted to assess the validity and reliability of the survey instrument. An email delivery method was used to implement the survey, and a 22% response rate was achieved (n=219). The majority of respondents were female (96%), white (89%), married (77%), currently working (86%), and had treated HIV/AIDS patients in private practice (80%). Bivariate analysis showed that dental hygienists' intentions toward treating HIV/AIDS patients were significantly associated with five independent variables, and binary logistic regression confirmed the significance of two of these associations. Overall, study participants indicated that they were willing to, and had positive attitudes toward, clinically treating HIV/AIDS patients; they were confident in their ability to treat them, and their normative beliefs did not hinder their intention to do so, and they did not worry about acquiring HIV in the workplace. Three recommendations were made: increase access to oral health care for HIV/AIDS patients within community settings by removing barriers to care, incorporate cultural/sensitivity training in all dental/dental hygiene school curriculums, and mandate Florida HIV/AIDS continuing education requirements every biennium for dentists and dental hygienists.

abstract: Understanding how adherence affects outcomes is crucial when developing and assigning interventions. However, interventions are often evaluated by conducting randomized experiments and estimating intent-to-treat effects, which ignore actual treatment received. Dose-response effects can supplement intent-to-treat effects when participants are offered the full dose but many only receive a partial dose due to nonadherence. Using these data, we can estimate the magnitude of the treatment effect at different levels of adherence, which serve as a proxy for different levels of treatment. In this dissertation, I conducted Monte Carlo simulations to evaluate when linear dose-response effects can be accurately and precisely estimated in randomized experiments comparing a no-treatment control condition to a treatment condition with partial adherence. Specifically, I evaluated the performance of confounder adjustment and instrumental variable methods when their assumptions were met (Study 1) and when their assumptions were violated (Study 2). In Study 1, the confounder adjustment and instrumental variable methods provided unbiased estimates of the dose-response effect across sample sizes (200, 500, 2,000) and adherence distributions (uniform, right skewed, left skewed). The adherence distribution affected power for the instrumental variable method. In Study 2, the confounder adjustment method provided unbiased or minimally biased estimates of the dose-response effect under no or weak (but not moderate or strong) unobserved confounding. The instrumental variable method provided extremely biased estimates of the dose-response effect under violations of the exclusion restriction (no direct effect of treatment assignment on the outcome), though less severe violations of the exclusion restriction should be investigated. / Dissertation/Thesis / Doctoral Dissertation Psychology 2018

INTRODUÇÃO: A asma grave acomete menos de 10% dos asmáticos, mas tem um impacto desproporcional sobre a utilização de recursos de saúde, contribuindo para, pelo menos, metade dos custos diretos e indiretos da doença. A proporção de indivíduos obesos ou com sobrepeso é elevada em pacientes com asma grave. Na verdade, a obesidade é um fator de risco para a asma, está associada com a gravidade da doença, com pior resposta a corticosteroides e pior controle clínico. Estudos sobre os efeitos da perda de peso em pacientes com asma ainda são escassos. OBJETIVOS: Avaliar o impacto da perda de peso com medidas clínicas em pacientes com asma grave e obesidade. MÉTODOS: Este é um estudo prospectivo randomizado aberto com dois grupos paralelos. Os participantes eram obesos e com asma grave e que, depois de um período de run-in de três meses, não estavam controlados de acordo com critérios da GINA. Os pacientes elegíveis foram randomizados em uma proporção de 2:1 (perda de peso: controle). Todos os participantes passaram por consultas bimensais no ambulatório de asma e foram acompanhados por seis meses. O desfecho primário foi o nível de controle da asma seis meses após o início do programa de redução de peso medido pelo Questionário de Controle da Asma (ACQ). Os desfechos secundários incluíram o Teste de Controle da Asma (ACT), resultados de função pulmonar, o Questionário Respiratório de St. George (SGRQ), a mudança na reatividade brônquica à metacolina, o uso diário de medicação de alívio para asma, percentagem de dias livres de sintomas, número de visitas ao pronto-socorro e exacerbações, marcadores de inflamação das vias aéreas medidos pelo escarro induzido e pelo óxido nítrico exalado (FeNO). IgE, proteína C reactiva, eotaxina, leptina e Transforming Growth Factor beta 1 (TGF 1) também foram medidos. RESULTADOS: Trinta e três foram randomizados. O grupo era composto predominantemente de mulheres com obstrução moderada, aprisionamento de ar, aumento da resistência das vias aéreas e marcada eosinofilia no escarro. O aumento dos níveis séricos de IgE foram consistentes com uma predominância de asma atópica. Dos 22 pacientes randomizados para submeterem-se a tratamento para a obesidade, 12 atingiram a meta de perda de peso de, pelo menos, 10% do peso corporal. A redução de peso no grupo de tratamento foi associada com melhor controle da asma medido pelo ACQ, ACT e SGRQ. Houve aumento de dias sem sintomas, menor uso de medicação de resgate e menos visitas ao serviço de emergência durante o período de estudo. Não houve diferença no número de exacerbações. A capacidade vital forçada (CVF) aumentou significativamente no grupo de tratamento e permaneceu inalterada no grupo de controle. As outras medidas da função pulmonar não mostraram diferenças entre os grupos. A hiperreatividade das vias aéreas, níveis de óxido nítrico exalado e celularidade do escarro induzido não se alterou ao longo do estudo. Os níveis de leptina diminuíram em ambos os grupos. Os níveis séricos de IgE, proteína C-reactiva, eotaxina, e TGF-1 não se alteraram. CONCLUSÃO: Nosso estudo adiciona informações à controvérsia sobre o impacto da obesidade e seu tratamento no controle da asma. Nossos resultados sugerem que a redução de peso em pacientes obesos com asma grave melhore os resultados de asma por mecanismos não relacionados com a inflamação das vias aéreas e que o controle da asma pobre em pessoas obesas é, pelo menos em parte, o resultado de fatores relacionados com a obesidade. A abordagem terapêutica para pacientes obesos com dificuldade de tratar a asma deve ser destinada à redução de peso, bem como à intensificação do tratamento anti-inflamatório / INTRODUTION: Severe asthma affects less than 10% of asthmatics, but has a disproportionate impact on the use of health resources, contributing to at least half of the direct and indirect costs of the disease. The proportion of obese or overweight individuals is elevated in patients with severe asthma. In fact, obesity is a risk factor for asthma, is associated with the severity of the disease, a poor response to corticosteroids and worse clinical control. Studies on the effects of weight loss in patients with asthma are still scarce. OBJECTIVES: Assess the impact of weight loss with a medical weight loss program in patients with severe asthma associated with obesity. METHODS: This is a prospective open study with two randomized parallel groups. The participants were obese and with severe asthma and, after a three month run-in period, were not controlled according to GINA criteria. Eligible patients were randomized in a 2:1 ratio (weight loss:control). All participants attended bimonthly consultations in the asthma clinic and were followed for six months. The primary outcome measure was the level of asthma control 6 months after initiation of the weight reduction program quantified by using the Asthma Control Questionnaire (ACQ). Secondary clinical outcomes included the Asthma Control Test (ACT), lung function results, score on the St. Georges Respiratory Questionnaire (SGRQ), change in metacholine reactivity, daily use of asthma reliever medication, percentage of asthma symptom free days, number of visits to emergency room and exacerbations, markers of airway cellular inflammation measured in induced sputum and with exhaled nitric oxide (FeNO). IgE, C reactive protein, leptin, eotaxin and Transforming Growth Factor beta 1 (TGF1) levels in serum were also measured. RESULTS: Thirty-three patients were randomized. The group consisted predominantly of women with moderate airflow obstruction, air trapping, increased airway resistance and marked eosinophilia in the sputum. The increased serum levels of IgE were consistent with a predominance of atopic asthma. Of the 22 patients randomized to undergo treatment for obesity, 12 achieved the weight loss goal of at least 10% of body weight. The reduction in weight in the treatment group was associated with improvement in the control as measured by ACQ, ACT and SGRQ. There was increase of symptom-free days, less use of rescue medication and fewer visits to the emergency room during the study period. There were no differences in the number of exacerbations. The forced vital capacity (FVC) increased significantly in the treatment group and remained unchanged in the control group. The other measures of the pulmonary function showed no differences between groups. The airway hyperresponsiveness, exhaled nitric oxide levels and induced sputum cellularity did not change throughout the study. Leptin levels decreased in both groups. Serum levels of IgE, C-reactive protein, eotaxin, and TGF-1 did not change. CONCLUSION: Our study adds information to the controversy about the impact of obesity and its treatment on asthma control. Our results suggest that weight reduction in obese patients with severe asthma improves asthma outcomes by mechanisms not related to airway inflammation and that poor asthma control in people who are obese is at least in part the result of obesity-related factors. The therapeutic approach for obese patients with difficult-to-treat asthma should therefore be aimed at weight reduction as well as on intensifying antiinflammatory treatment

Les résultats d’un nombre croissant d’études montrant l'effet préventif du traitement antirétroviral(TARV) sur la transmission du VIH ont jeté les bases de travaux de modélisation suggérant que ledépistage universel et répété du VIH, associé à l'initiation immédiate d’un TARV chez les personnesséropositives, pourraient infléchir l'épidémie de VIH, en particulier en Afrique sub-saharienne. On nesait pas encore si cette stratégie, qui consiste à Tester et Traiter Universellement (TTU), est réalisableau niveau populationnel, compte tenu des contraintes et du niveau requis de prise en charge du VIH quisont sans précédent.L'objectif de cette thèse était d'explorer les conditions de mise en oeuvre d’une stratégie TTU à largeéchelle. Sur la base des protocoles d'études communautaires menées en Afrique subsaharienne, nousavons caractérisé la diversité des approches TTU. Dans le cadre de l'une de ces études, l'essai ANRS12249 TasP mené dans une zone rurale d’Afrique du Sud, nous avons décrit les expériences etperceptions des travailleurs de la santé vis-à-vis de la stratégie TTU et étudié les trajectoires de soinsdes personnes vivant avec le VIH.Les résultats rapportés dans cette thèse mettent en évidence que les stratégies TTU englobent une variétéd'interventions de prise en charge du VIH, rendant complexe l'évaluation de leur impact sur l'épidémie.Les analyses des opinions des travailleurs de santé et des comportements des patients exposés à unestratégie TTU ont également permis de souligner le potentiel de la stratégie à faire évoluer les pratiquesprofessionnelles et l’accès aux soins des patients. L’ensemble de ce travail permet de mieux appréhenderles efforts nécessaires pour assurer un impact maximal d’une stratégie TTU sur la santé des populationsen Afrique subsaharienne. / Increasing evidence of the preventive effect of antiretroviral treatment (ART) on HIV transmission havelaid the foundations for mathematical models to suggest that universal and repeated HIV testing,combined with immediate initiation of ART among those diagnosed HIV-positive could curtail the HIVepidemic, especially in sub-Saharan Africa. It is still unknown if this strategy, labelled as “UniversalTest and Treat” (UTT), could be workable at population level, given the unprecedented HIV servicesuptake rates that it requires.The objective of this thesis was to explore the terms of large-scale UTT implementation. Based on theprotocols of community-based trials conducted in sub-Saharan Africa, we characterized the diversity ofUTT approaches. Within the framework of one of those studies, the ANRS 12249 TasP trial, conductedin rural South Africa, we described the perceptions of health care workers regarding UTT and studiedthe care trajectories of people living with HIV from care referral to viral suppression.The findings reported in this thesis highlight that UTT strategies encompass a variety of healthinterventions, challenging the assessment of their impact on the HIV epidemic. Analyses of health careworkers opinions and patients’ behaviours when exposed to UTT underlined the potential of the strategyto change professional practices and patients’ access to care. Overall this work provides some insightson the efforts needed to allow the maximal public health impact of UTT in sub-Saharan Africa.

B-NHLs sind eine heterogene Gruppe lymphoproliferativer Neoplasien mit unterschiedlichen Krankheitsverläufen und Therapieansprechen. Trotz fortschrittlicher neuer Therapien, erleiden 20-30 % der Patienten ein Rezidiv / Progress des NHL. Für diese Patientengruppe ist die ASZT weiterhin die Standardtherapie mit kurativem Ansatz. Die vorliegende Arbeit stellt eine retrospektive unizentrische Analyse von konsekutiven Patienten dar (N=148), die aufgrund eines malignen B-NHL im Rahmen einer Konsolidierung oder Salvagesituation ein oder zwei Zyklen Dexa-BEAM (Dexamethason, Carmustin (BCNU), Etoposid, Cytarabin, Melphalan) Chemotherapie mit der Intention einer anschließenden ASZT am Universitätsklinikum Leipzig erhalten haben. Machbarkeit der ASZT - Intention-to-treat-Analyse 106 von 148 Patienten (72 %) erhielten die ASZT. Bei 42 Patienten (28 %) wurde die geplante ASZT nicht durchgeführt (29 Patienten (20 %) sind nach dem 1. Dexa-BEAM und 13 Patienten (9 %) nach dem 2. Dexa-BEAM Zyklus ausgeschieden). Die Hauptgründe für das Abrücken von der ursprünglich geplanten ASZT waren Nicht-Ansprechen auf Dexa-BEAM [N = 16/148 (11 %)], therapiebedingte Morbiditäten [N = 15/148 (10 %)] und erfolglose Stammzellmobilisation im Rahmen der Dexa-BEAM Chemotherapie [N = 8/148 (5 %)]. Faktoren mit einer statistischen Signifikanz, die für eine tatsächliche Durchführung der geplanten ASZT sprachen waren: Alter < 51 Jahre bei Erstdiagnose (ED) (p = 0,039), Vorhandene B-Symptome bei ED (p = 0,004), weniger als zwei Vortherapien vor Dexa-BEAM (p < 0,000), zwei Zyklen Dexa-BEAM bei vorhandener Chemotherapiesensitivität (p < 0,000) und der Remissionsstatus (CR oder PR) vor ASZT (p < 0,000). Das Therapieansprechen auf Dexa-BEAM und somit der Remissionsstatus vor ASZT stellten sich in der multivariaten Analyse als einflussreichste Prognosefaktoren für eine tatsächliche Durchführung der geplanten ASZT heraus (p < 0,000; HR 23,3). Dabei zeigte sich kein Unterschied zwischen einer kompletten oder partiellen Remission. Keinen Einfluss auf die Durchführung der ASZT hatten die Parameter: Entität des NHL (indolent vs. aggressiv), Stadium der Erkrankung, Knochenmark (KM)- oder extranodaler Befall bei ED und Zeitintervall zwischen ED bis zur Dexa-BEAM Therapie. Ein Zyklus versus zwei Zyklen Dexa-BEAM vor ASZT 60 Patienten (40 %) erhielten einen Zyklus und 88 Patienten (60 %) zwei Zyklen Dexa-BEAM vor der geplanten ASZT. Der Remissionsstatus vor Dexa-BEAM und die entsprechende Therapieindikation hatten einen hochsignifikanten Einfluss auf die Anzahl der Dexa-BEAM Zyklen (p < 0,000). Patienten mit einem indolenten NHL in erster Remission erhielten einen Zyklus Dexa-BEAM mit nachfolgender ASZT als Konsolidierungstherapie. Hingegen erhielten Patienten im Rezidiv bzw. mit primär refraktärer Erkrankung zwei Zyklen Dexa-BEAM als 'Salvagetherapie' vor ASZT. Alter, Performance-Status, B-Symptome bei ED und speziell ein KM-Befall zum Zeitpunkt der Dexa-BEAM Therapie hatten bei fehlender statistischer Signifikanz keinen Einfluss auf die Entscheidungsfindung 1 vs. 2 Zyklen Dexa-BEAM Chemotherapie. Das Ansprechen auf Dexa-Beam war exzellent: 91 % der vor Dexa-BEAM nicht in Remission (keine CR / PR) befindlichen Patienten erreichten eine Remission. Durch den ersten Zyklus Dexa-BEAM konnten 44/56 (79 %) nicht in Remission befindlichen Patienten in eine Remission (CR / PR) überführt werden; Durch den zweiten Zyklus konnte bei weiteren 19 Patienten eine CR erreicht werden. Stellenwert der ASZT für das Outcome Nach einer medianen Nachbeobachtung von 51 Monaten, betrugen das mediane Gesamtüberleben (OS) und das progressionsfreie Überleben (PFS) 9,5 Jahre. Nicht überraschend lagen beide bei der transplantierten Kohorte deutlich höher im Vergleich zur nicht-transplantierten Gruppe (p < 0,000). Univariat, erwiesen sich Alter > 50 Jahre, nicht Erreichen einer Remission zum Zeitpunkt der ASZT, ein KM-Befall zum Zeitpunkt der ASZT als relevante Faktoren mit einer negativen Auswirkung auf OS und PFS. Interessanterweise waren die Ergebnisse der ASZT (OS und PFS) bei Patienten in PR und CR vergleichbar (p = 0,23), Ein KM-Befall zum Zeitpunkt der ASZT aber nicht ein Befall zur ED bzw. vor Dexa-BEAM hatte einen hochsignifikanten Einfluss auf das Gesamtüberleben (p = 0,001) (65 % 10-Jahres-Überlebensrate ohne KM-Befall versus 15 % bei KM-Befall vor ASZT). Erwartungsgemäß war das 5-Jahres-OS (85 %) und insbesondere das PFS (67 %) bei Patienten mit der Indikation der ASZT als Konsolidierung höher im Vergleich zu Patienten die eine ASZT als Salvagetherapie erhielten [OS 74 % (p = 0,09); PFS 34 % (p = 0,004)]: Die Anzahl der Vortherapien, vorangegangene Behandlung mit Rituximab oder Anzahl der Dexa-BEAM Zyklen hatten keinen Einfluss auf das Überleben. In der Multivariat Analyse, zeigten sich der Remissionsstatus (CR / PR) vor ASZT (p < 0,000) und der KM-Befall bei ASZT (p = 0,002) als einflussreichste Faktoren für das Überleben. Die Wahrscheinlichkeit nach fünf Jahren rezidivfrei zu sein lag bei 47 %. Analog zum OS und PFS, beeinflussten die Parameter Alter, Therapieindikation zur ASZT (Konsolidierung versus Salvage), der Remissionsstatus (CR / PR) und KM-Befall bei ASZT die Rezidivinzidenz (RI). Bezüglich des Remissionsstatus vor ASZT war es auch bei der RI unerheblich, ob eine komplette oder eine partielle Remission vorlag (p = 0,2). Insgesamt lag die therapiebedingte Mortalität bei 9,5 % (14/148). Unter Dexa-Beam verstarben 9/148 (6 %) Patienten. Fünf weitere Patienten verstarben unter der ASZT. Damit liegt die therapiebedingte Mortalität der ASZT bei 4.7 % (5/106 Patienten). Die Haupttodesursache waren Infektionen. Die ASZT ist trotz der neuen medikamentösen Entwicklungen bei Lymphomen weiter ein fester Bestandteil der Behandlung insbesondere im Rezidiv. Das Ansprechen auf Dexa-Beam, weniger die Stammzellapherese, ist der entscheidende Faktor für die tatsächliche Durchführung einer geplanten ASZT. Der fehlende Unterschied im Outcome nach ASZT bei Patienten mit PR im Vergleich zu CR nach Dexa-Beam stellt die Indikation eines zweiten Zyklus bei Patienten, die solch eine Remission bereits nach dem ersten Zyklus erreicht haben, in Frage.:Inhaltsverzeichnis 1 Einleitung 6 1.1 Non-Hodgkin-Lymphome - Definition 6 1.2 Klassifikation 6 1.3 Epidemiologie, Ätiologie, Pathogenese 7 1.4 Diagnostik 8 1.5 Stadieneinteilung 10 1.6 Behandlungsstrategien beim B-NHL 11 1.6.1 Therapie indolenter NHL 12 1.6.2 Therapie aggressiver NHL 16 1.7 Rolle der autologen Stammzelltransplantation als Konsolidierungs- oder Salvagetherapie 19 1.8 Fragestellung und Zielsetzung 22 2 Methoden 23 2.1 Übersicht 23 2.2 Remissionskriterien und Patienteneinteilung zur autologen Stammzelltransplantation 23 2.3 Dexa-BEAM Chemotherapie 24 2.4 Hochdosis-Chemotherapie und autologe Stammzelltransplantation 24 2.5 Toxizität 25 2.6 Nachbeobachtung ('Follow-up') 25 2.7 Datenerhebung und Definierung der Ereignisse 26 2.8 Statistische Auswertung 26 3 Ergebnisse 28 3.1 Übersicht 28 3.2 Ergebnisse vor autologer Stammzelltransplantation 30 3.2.1 Patientencharakteristika 30 3.2.2 Korrelationen 34 3.2.3 Machbarkeit der autologen Stammzelltransplantation - Intention-to-treat: 38 Transplantierte (Tx) vs. Nicht-transplantierte (NTx) Gruppe 38 3.2.4 Einzelne Betrachtung von relevanten Risikofaktoren für die Durchführbarkeit einer autologen Stammzelltransplantation 41 3.3 Ergebnisse nach autologer Stammzelltransplantation (Outcome) 47 3.3.1 Gesamtüberleben - Overall Survival (OS) 47 3.3.2 Progressionsfreie Überleben (PFS) 52 3.3.3 Non-Relapse-Mortality (NRM) - Therapiebedingte Mortalität 56 3.3.4 Rezidivinzidenz (RI) 57 3.3.5 Multivariate Analyse 58 4 Diskussion 60 4.1 Überblick 60 4.1.1 Aussagekraft der vorliegenden Ergebnisse 60 4.1.2 Schwachpunkte der Analyse 60 4.2 Machbarkeit der autologen Stammzelltransplantation - Prognosefaktoren 61 4.3 Rolle der Dexa-BEAM Chemotherapie: 1 vs. 2 Zyklen 62 4.4 Outcome der autologen Stammzelltransplantation - Prognosefaktoren 63 4.5 Autologe Stammzelltransplantation als Konsolidierung- vs. Salvagetherapie 65 4.6 Rolle der autologen Stammzelltransplantation in Hinblick auf die neuen Medikamente 67 5 Zusammenfassung 68 6 Literaturverzeichnis 71 7 Anhang 77 8 Selbstständigkeitserklärung 83 9 Tabellarischer Lebenslauf 83 10 Danksagung 84