Depression has been cited as the most prevalent of the Axis I disorders affecting upward of 16% of American adults in their lifetimes (Kessler et al., 2005). The literature on effective treatments for depression is substantial, however the follow-up literature that speaks to what happens after treatment ends is much smaller. This thesis describes two studies. The first is an overview of reviews of post-treatment outcomes for adults treated for major depressive disorder (MDD). The second is a narrative systematic review of studies of long-term (at least 12 months) post-treatment outcomes after the completion of treatment for major depressive disorder (MDD). These studies synthesize the available evidence concerning post-treatment outcomes and discuss the limitations of these data. Relapse is a significant issue for many people who respond to treatment with upwards of 50% of people relapsing within a year of the end of treatment, depending on the type of treatment. Some treatments have significant relapse prevention effects, including continued medication treatment, acute and continuation phase CBT, and variations of CBT designed specifically for addressing residual symptoms after acute treatment or specifically aimed at relapse prevention. Given that the risk of relapse after treatment is significant, it should be discussed during acute treatment, as should approaches to reducing the risk of relapse. Recommendations for future research are discussed. Within the overview of reviews, there was considerable consistency across reviews which aided in the formulation of practical recommendations for clinicians and for patients. Examples include provision of education about the probability of relapse and planning for relapse prevention during acute phase treatment. Engaging in continuation and maintenance treatments that are aimed at reducing relapse, and whenever possible, continuing treatment until patients are considered to be in recovery, and not just for a certain period of time, or until the point of remission of symptoms are also recommended to reduce rates of relapse.

Background: Fibromyalgia (FM) disorder commonly involves musculoskeletal widespread pain and other symptoms like fatigue, sleep disruption, depression and anxiety and is associated with disability, work disability and high health care utilization. An integrated approach combining pharmacological and non-pharmacological treatments is advised to manage the disorder. Among the non-pharmacological interventions exercise has been shown to help; however, details about effectiveness of different types of interventions remain unknown. Objectives: The objective of this dissertation was to synthesize the evidence on the effectiveness of: a) Aquatic exercise interventions for adults with FM as reported in randomized control trials (RCTs), and b) any physical activity interventions for adults with FM as reported in systematic reviews. This was done by conducting a Cochrane systematic review of an aquatic training intervention and second, synthesizing the effectiveness of a variety of exercise interventions. Methods: For the Cochrane systematic review, nine electronic databases were searched. Selection criteria included full text publication of a RCT including an aquatic exercise intervention (AQ) (exercise in water was >50% of the full intervention) and provision of between-group outcome data. Pairs of reviewers independently screened and selected articles, assessed risk of bias, and extracted data on 24 outcomes. Effects of the interventions were evaluated using mean, standardized mean differences and 95% confidence interval (MD/SMD [95% CI]). Specific computer software designed for meta-analysing and evaluating the quality of evidence were used (i.e RevMan, GradePro). The second review, the synthesis of a variety of exercise interventions or umbrella systematic review, inspected six electronic databases for the January 1st 2007 to March 31st 2012 period. We included systematic Cochrane and non-Cochrane reviews that reported on the effects of any physical activity intervention for adults with FM. Pairs of reviewers independently screened and selected articles, assessed quality of the reviews using a valid and reliable tool (AMSTAR tool), and extracted data on four outcomes. Effects of the interventions were evaluated using standardized mean differences and 95% confidence intervals (SMD [95% CI]). We planned to use RevMan software for meta-analysis but due to heterogeneity of the reviews this was not done. Results: The Cochrane review examined 16 aquatic exercise training studies (n = 881). Nine studies compared aquatic exercise to control, five studies compared aquatic exercise to land-based exercise, and two compared aquatic to a different aquatic program. The aquatic vs control studies provided low to moderate quality evidence suggesting that aquatic training is beneficial for wellness, symptoms and fitness in adults with FM. The aquatic vs land group results suggested very low to low quality evidence that there are no differences in benefits between aquatic and land-based exercise except in muscle strength (very low quality evidence favoring land). In examining aquatic vs aquatic meta-analyses was not possible and only one difference in a major outcome was found. The umbrella systematic review synthesis of information (n-= nine systematic reviews) found positive results for diverse exercise interventions on pain, multidimensional function, and self-reported physical function and no conclusive evidence for new (to FM) physical activity mode (i.e. qigong, tai chi). There are however, methodological weaknesses in some of the reviews which reduce applicability of the research to clinical practice. Adverse effects reported suggest there was no serious harm performing physical activity for individuals with FM. Conclusions: Exercise interventions have the potential to positively impact individuals with FM including several outcomes like quality of life, physical functioning and pain. While some interventions had statistically significant results, methodological limitations prevented us from arriving at conclusions regarding particular elements and modes of exercise that will help inform health professional’s clinical practice. On the other hand, some preliminary analysis showed that variables like age, disease duration, disease severity and pain intensity warrant further exploration. A rigorous scientific process (or quality research) as the precursor of quality evidence is crucial for validity and credibility of the information and our future understanding of the effectiveness of exercise interventions for individuals with FM.

Background: A compilation of high quality systematic reviews (SRs) on lifestyle factors associated with adult glioma and meningioma was developed. Methods and Materials: Phase 1 consisted of a systematic overview of existing SRs. For Phase 2, high quality SRs were incorporated in an update. Moderate or low quality SRs which had not been considered in a high quality review were eligible for a de-novo synthesis. Results: Phase 1 resulted in seven moderate to low quality reviews. From this, in Phase 2, smoking, mobile phone and hair dye use were subjected to de-novo reviews. For smoking, it was suggestive that past smokers had an increased risk. For mobile phone use, there was no overall association, however it was suggestive that ipsilateral and high cumulative call time were associated with slight increased risk. No association was observed for personal hair dye use. Conclusions: Despite these null associations, rigorous SR methods were used providing confidence in conveying these results.

Depression has been cited as the most prevalent of the Axis I disorders affecting upward of 16% of American adults in their lifetimes (Kessler et al., 2005). The literature on effective treatments for depression is substantial, however the follow-up literature that speaks to what happens after treatment ends is much smaller. This thesis describes two studies. The first is an overview of reviews of post-treatment outcomes for adults treated for major depressive disorder (MDD). The second is a narrative systematic review of studies of long-term (at least 12 months) post-treatment outcomes after the completion of treatment for major depressive disorder (MDD). These studies synthesize the available evidence concerning post-treatment outcomes and discuss the limitations of these data. Relapse is a significant issue for many people who respond to treatment with upwards of 50% of people relapsing within a year of the end of treatment, depending on the type of treatment. Some treatments have significant relapse prevention effects, including continued medication treatment, acute and continuation phase CBT, and variations of CBT designed specifically for addressing residual symptoms after acute treatment or specifically aimed at relapse prevention. Given that the risk of relapse after treatment is significant, it should be discussed during acute treatment, as should approaches to reducing the risk of relapse. Recommendations for future research are discussed. Within the overview of reviews, there was considerable consistency across reviews which aided in the formulation of practical recommendations for clinicians and for patients. Examples include provision of education about the probability of relapse and planning for relapse prevention during acute phase treatment. Engaging in continuation and maintenance treatments that are aimed at reducing relapse, and whenever possible, continuing treatment until patients are considered to be in recovery, and not just for a certain period of time, or until the point of remission of symptoms are also recommended to reduce rates of relapse.

This manuscript-style dissertation consists of three publications interconnected in their focus on the dynamically evolving use of immersive virtual reality technologies for language education. The manuscripts included in this dissertation were adapted from three research papers published or submitted for publication in scientific journals and book chapters. The first manuscript provides an overview of immersive technologies of different levels of immersion, ranging from 2D displays on a flat screen to highly immersive interactive experiences rendered in virtual reality using head-mounted displays. The second manuscript is a systematic review, and it narrows down the scope of immersive technologies outlined in the previous publication by exploring existing research on the technologies related to the highest level of immersion for language learning, namely the high-immersion virtual reality technologies. The third manuscript continues to investigate the application of those technologies for language learning, but the focus is shifted from examining virtual reality applications to exploring language teachers' beliefs about using those technologies. This dissertation offers a comprehensive overview of high-immersion virtual reality use for language learning which may serve as an ideal starting point for researchers and educators interested in learning more about the current state of virtual reality integration in schools from the perspectives of both language learners and teachers.

Submitted in partial compliance with the requirements for the Master’s Degree in Technology: Chiropractic, Durban University of Technology, 2014. / Background: Practitioners are required to practice evidence-based medicine. The availability of large volumes of information make this practice style difficult for the practitioner. However, a systematic review allows literature to be organised, rated and allows current, abbreviated research resources for practitioner in clinical practice. Objectives: The effectiveness of the Gonstead Chiropractic Technique (GCT) was evaluated to present current evidence available for various conditions for which the GCT is utilised in clinical practice. Thus, the aim of the study was to systematically review, collate and evaluate the research evidence in the literature to determine the effectiveness of the GCT. Method: A literature search was conducted, based on key terms including: Gonstead and manual, Gonstead and technique, and Gonstead and manipulative/manipulation. Databases searched were: CINAHL Plus, Google Scholar, MEDLINE, Metalib, Pubmed, Science Direct, Springerlink and Summons. The articles were screened according to inclusion and exclusion criteria, after which secondary hand and reference searches were done. Thereafter the articles were reviewed by six independent reviewers. Appropriate scales were used to rate the methodological rigour of each article (e.g. PEDro). The results were analysed and ranked, before these outcomes were classified and contextualised in the clinical conditions on which the included studies were based. Results: A total of 477 citations were identified; after screening 26 English articles remained. Two articles were added through the secondary hand-search. Limited to no evidence existed for the effectiveness of GCT for neck pain / headache / face pain and limited evidence existed for gynaecological issues, scoliosis, neurological disorders, fractures, blood pressure and physiological presentations. Consensus was evident for gynaecological issues, neurological disorders, fractures (with the exception of the undiagnosed fracture) and physiological presentations, whereas the neck pain / headache / face pain and scoliosis were conflicting. Conclusion: Limited evidence shows a need for future studies with stringent methodological rigour, so as to investigate the appropriateness / inappropriateness of the use of the GCT. The lack of evidence for GCT may compromise appropriate informed consent and treatment. Therefore practitioners are encouraged to use appropriate and validated tools to measure the patient’s clinical progress

The objective of the work presented in this thesis was to explore the role of potential alternatives to platelet transfusions and specifically to investigate whether desmopressin could be used for treatment of thrombocytopenia or platelet dysfunction. Patients with thrombocytopenia or platelet dysfunction are often treated with platelet transfusions to treat or prevent bleeding. However the evidence for the efficacy of platelet transfusion is limited and there is some evidence of harm. I have focused on thrombocytopenic patients with haematological malignancies or critically ill patients, who are amongst the groups most commonly treated with platelet transfusions. The aims of this research were to determine: 1. If levels of Von Willebrand factor (VWF) or other measures of haemostasis are predictive of bleeding in severe thrombocytopenia; 2. Whether VWF compensates for thrombocytopenia in vitro; 3. The evidence for the efficacy of desmopressin in all patients undergoing surgery or invasive procedures; 4. The evidence for desmopressin for platelet dysfunction or thrombocytopenia; 5. If it is feasible to use desmopressin to treat critically ill thrombocytopenic patients in a clinical trial. To identify derangements of haemostasis that may signify candidates for alternatives to platelet transfusions, I analysed blood samples from an observational trial of fifty patients with haematological malignancies and profound thrombocytopenia due to intensive chemotherapy. I used a panel of tests to investigate measures of primary haemostasis, thrombin generation, cross-linked fibrin formation and fibrinolysis. Using multivariable logistic regression, I found no consistent correlation between any measures of haemostasis and the risk of clinically significant bleeding. VWF antigen levels were the best predictor of clinically significant bleeding on the same day (odds ratio 0.31, 95% confidence interval 0.10 to 0.98, p=0.047) but were not predictive of severe bleeding over the 24 hours after the test (odds ratio 0.48, 95% confidence interval 0.10 to 2.34, p=0.36). In a separate set of experiments, I evaluated thrombus formation under flow in thrombocytopenia. This technique was sensitive to the platelet count . Addition of exogenous VWF to thrombocytopenic blood resulted in improvement in thrombus formation, suggesting that agents that affect or influence VWF pathways might have a role. Desmopressin can be used to increase VWF levels, so leading on from my laboratory experiments; I used systematic reviews and meta-analyses to assess whether desmopressin could be used in unselected patients to reduce bleeding peri-operatively. I identified 62 randomised controlled trials. Overall there was no evidence of benefit for administering desmopressin to unselected patients. However further analysis of eleven randomised controlled trials that focused on patients with platelet dysfunction found that desmopressin resulted in transfusion of fewer units of red cells (equivalent to a 25% reduction compared to control), less blood loss (equivalent to a 23% reduction compared to control) and a lower risk of requiring a re-operation due to bleeding (Peto odds ratio 0.39, 95% confidence interval 0.18 to 0.84). There was no evidence for an increase in thrombotic events. There was no randomised controlled trial evidence for perioperative desmopressin for patients with thrombocytopenia. These specific research gaps were addressed by designing new clinical trials. I have commenced a randomised controlled feasibility trial of desmopressin versus placebo for critically ill patients with thrombocytopenia undergoing invasive procedures. This trial is ongoing and is the first randomised trial evaluating peri-procedural desmopressin in thrombocytopenia. The programme of work arising from this research has the potential to benefit a large number of patients by preventing bleeding and reducing exposure to allogeneic blood components such as platelets. The results presented in this thesis are exploratory but are an important step on a path towards larger trials using desmopressin as an alternative, or adjunct to platelet transfusion.

Orientador: Vania dos Santos Nunes Nogueira / Resumo: Objetivo: esta revisão sistemática da literatura e metanálise comparou a taxa da mortalidade na acromegalia com a taxa esperada na população geral dos estudos publicados antes de 2009 versus estudos publicados após. Métodos: foram criadas três estratégias de busca gerais e adaptáveis às bases de dados eletrônicas na área da saúde: Embase (1980–2015), Pubmed (1966–2016) e Biblioteca Virtual da Saúde (1982–2016). Foram incluídos estudos observacionais em que a mortalidade na acromegalia foi comparada à da população geral, por meio do número de mortes observadas nessa doença em comparação à taxa de mortalidade esperada para população geral (O/E). A partir do O/E, recalculamos todos os Standardized Mortality Ratio (SMR) e os seus respectivos intervalos de confiança (IC) que foram plotados em uma metanálise. Resultados: foram identificadas 1005 referências, dois revisores independentemente leram os títulos e resumos desses artigos. Dos 27 estudos potencialmente elegíveis, 23 foram incluídos e quatro foram excluídos por não preencherem os critérios de elegibilidade. A mortalidade geral na acromegalia foi significativamente superior a da população geral (SMR: 1,66, IC 1,44 - 1,93, p < 0,00001, I2 84%). Separando os artigos publicados a partir de 2009, a mortalidade na acromegalia não foi significativamente diferente 1,29 (IC 0,95-1,76, p=0,10, I2 86%). Nas análises por subgrupo de acordo com o status da doença, sete estudos consideraram como curados os pacientes que apresentaram a n... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Objective: This systematic literature review and meta-analysis compared the mortality rate in acromegaly with the expected rate in the general population of studies published before 2009 versus studies published after. Methods: three general and adaptive search strategies were created from the electronic databases in the health area: Embase (1980-2015), Pubmed (1966-2016) and Virtual Health Library. Observational studies were included in which the mortality in acromegaly was compared to the general population, the number of deaths observed compared to the expected mortality rate in the general population (O/E). From O/E, we recalculated all the Standardized Mortality Ratio (SMR) and their respective confidence intervals (CI) that were plotted in a meta-analysis. Results: 1005 references were identified and two reviewers independently read the titles and abstracts of these articles. Of the 27 potentially eligible studies, 23 were included and four were excluded because they did not meet the eligibility criteria. Overall mortality in acromegaly was significantly higher than the general population (SMR: 1.66, CI 1.44 - 1.93, p <0.00001, I² 84%). Analyzing articles published as of 2009, the mortality in acromegaly was not significantly different, SMR 1.29 (CI 0.95-1.76, p = 0.10, I² 86%). In subgroup analyzes according to disease status, seven studies considered patients with IGF-1 normalization associated with random GH <2.5 ng / mL as cured. In these individuals, the SMR was 0.... (Complete abstract click electronic access below) / Mestre

Orientador: Marcos da Cunha Lopes Virmond / Resumo: Introdução: Indivíduos que estão em estreita associação ou proximidade com pacientes com hanseníase têm maior chance de adquirir a doença. A eficácia da quimioprofilaxia na prevenção da hanseníase nos contatos dos pacientes afetados para um ótimo controle da doença ainda não é clara. Métodos: pesquisas eletrônicas de Medline, EMBASE, CENTRAL e LILACS até outubro de 2017 foram realizadas para identificar estudos elegíveis. As listas de referência de estudos potencialmente elegíveis foram revisadas. Incluímos ensaios clínicos randomizados (RCTs) que compararam a quimioprofilaxia com placebo para a prevenção da infecção da hanseníase em contatos de pacientes afetados. O par de revisores examinou de forma independente artigos elegíveis, extraiu dados e avaliou o risco de viés. A abordagem GRADE foi utilizada para avaliar a certeza geral da evidência. Resultados: seis ECRs, incluindo 52.483 participantes, se mostraram elegíveis. Os resultados sugeriram uma redução estatisticamente significativa na hanseníase clínica em contatos até dois anos (Rácio de Risco (RR) 0,32, Intervalo Confidencial (IC) 0,11 0,62; p <0,0007; I2 = 70%, p = 0,07; evidência de qualidade) e de dois a cinco anos de seguimento (RR 0,51, IC 95% 0,29, 0,89; p = 0,02; I2 = 80%, p <0,0005; evidência de baixa qualidade) com o uso de 6 quimioprofilaxia em comparação com placebo. No entanto, os resultados sugeriram uma redução não significativa na hanseníase clínica nos contatos ao longo de cinco anos (RR 0,77, IC 95%... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: Individuals who are in close association or proximity with leprosy patients have a greater chance of acquiring the disease. The effectiveness of chemoprophylaxis in preventing leprosy in contacts of affected patients for optimal disease control remains unclear. Methods: Electronic searches of Medline, EMBASE, CENTRAL, and LILACS up to October 2017 were conducted to identify eligible studies. Reference lists of potentially eligible studies were reviewed. We included randomized controlled trials (RCTs) comparing chemoprophylaxis with placebo for the prevention of leprosy infection in contacts of affected patients. Pair of reviewers independently screened eligible articles, extracted data, and assessed risk of bias. The GRADE approach was used to rate overall certainty of the evidence. Results: Six RCTs including 52,483 participants proved eligible. Results suggested a statistically significantly reduction in clinical leprosy in contacts both up to two years (Risk Ratio (RR) 0.32, 95% Confidential Interval (CI) 0.17, 0.62; p < 0.0007; I 2 =70%, p=0.07; low-quality evidence) and from two to five years of follow-up (RR 0.51, 95% CI 0.29, 0.89; p=0.02; I 2 =80%, p < 0.0005; low-quality evidence) with the use of chemoprophylaxis in comparison to placebo. However, results suggested a non-significant reduction in clinical leprosy in contacts over five years (RR 0.77, 95% CI 0.46, 1.28; p =0.31; I 2 =48%, p=0.16; low-quality evidence). Conclusions: Low-quality evidence show... (Complete abstract click electronic access below) / Mestre

Orientador: Vânia dos Santos Nunes-Nogueira / Resumo: Introdução: Existem quatro medicações disponíveis como tratamento complementar da doença de Cushing: pasireotida, cabergolina, cetoconazol e mifepristone. Contudo, não existe um consenso sobre qual medicação é mais efetiva e segura para o controle dessa neoplasia. Objetivo: comparar a segurança e a efetividade destas quatro medicações no controle de indivíduos com doença de Cushing não curados pela cirurgia, recidivados ou que não puderam realizar esse procedimento. Metodologia: para isso foi realizada uma revisão sistemática de acordo com a metodologia da colaboração Cochrane, no qual seriam incluídos estudos randomizados das comparações destas medicações entre si e fossem avaliados como desfechos primários a remissão do hipercortisolismo por meio da normalização do cortisol livre urinário (CLU), melhora na qualidade de vida, frequência de eventos adversos, melhora das comorbidades e sintomas associadas a essa doença. Foram realizadas três estratégias de busca adaptadas as bases eletrônicas de saúde: EMBASE, PubMed e CENTRAL-Cochrane. Os estudos foram selecionados por dois revisores independentes e os dados extraídos a partir de um formulário padronizado. Resultados: Foram incluídos dez estudos randomizados, um comparando cabergolina versus cetoconazol, e nove avaliando doses diferentes do pasireotida, sendo que oito se referiam ao mesmo protocolo de estudo. A normalização do CLU em seis meses de tratamento foi inferior na cabergolina em relação ao cetoconazol (33% versus 62... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre