Submitted by Biblioteca da Faculdade de Farmácia (bff@ndc.uff.br) on 2017-03-21T18:41:19Z No. of bitstreams: 1 Andrade, Thays Santos de [Dissertação, 2014].pdf: 467886 bytes, checksum: 9f9c6acd0d2516bb655fb10868b2db29 (MD5) / Made available in DSpace on 2017-03-21T18:41:19Z (GMT). No. of bitstreams: 1 Andrade, Thays Santos de [Dissertação, 2014].pdf: 467886 bytes, checksum: 9f9c6acd0d2516bb655fb10868b2db29 (MD5) / O câncer de mama é o tipo que mais acomete as mulheres em todo o mundo. Aproximadamente 30-50% dos pacientes diagnosticados nos estágios iniciais desenvolverão doença metastática, considerada incurável. Nesta fase da doença, as terapias objetivam prolongar a sobrevida e proporcionar controle paliativo dos sintomas. O trastuzumabe, um anticorpo monoclonal dirigido contra o receptor do fator de crescimento epidérmico humano (HER2), vem aumentando as taxas de respostas, sobrevida livre de progressão e/ou sobrevida global no câncer de mama, tendo sido recentemente incorporado pelo Sistema Único de Saúde (SUS) para tratamento de câncer de mama inicial e localmente avançado. O objetivo deste trabalho foi realizar uma revisão sistemática de avaliações de custo-efetividade do trastuzumabe em pacientes com câncer de mama metastático com superexpressão de HER2. Foram realizadas buscas, entre o período de 1998 a 2013, em seis bases de dados eletrônicas, duas ferramentas de busca na internet, além de pesquisa manual de referências. Foram considerados artigos em inglês, espanhol e português, sendo excluídos comentários, editoriais, cartas, estudos de caso, artigos de revisão, revisões sistemáticas e metanálises. As etapas de seleção dos estudos e extração dos dados foram realizadas por dois revisores independentes, e dúvidas foram resolvidas por um terceiro revisor. Os estudos foram avaliados em relação à qualidade seguindo abordagens empregadas por Teerawattananon et al. (2007). A análise dos dados foi realizada a partir da conversão dos custos e de observações das razões incrementais de custo-efetividade do trastuzumabe. Foram identificados 521 estudos, todos em inglês. Destes, descartou-se 455 (294 por não atenderem os critérios da revisão e 161 duplicatas). Sessenta e seis estudos foram incluídos para leitura dos resumos, resultando em 24 para leitura completa do texto. No total, 13 estudos compuseram esta revisão. Os esquemas terapêuticos adotados nas análises de custo-efetividade foram variados. Oito estudos compararam o tratamento do trastuzumabe como 1ª linha para doença metastática e cinco estudos como 2ª linha, sendo que três destes utilizaram o trastuzumabe como comparador na avaliação econômica e não como intervenção. Todos os estudos que utilizaram o trastuzumabe como 2ª linha de tratamento, não consideraram a intervenção custo-efetiva. Em relação à qualidade dos estudos incluídos, estes apresentaram uma boa qualidade, visto que a maioria cumpriu as diretrizes metodológicas de avaliação de custo-efetividade e utilizaram boas evidências na estimativa dos parâmetros. Finalmente, as análises utilizaram diferentes limiares para determinar se o tratamento com o trastuzumabe foi custo-efetivo, bem como diferenças na modelagem dos custos, desfechos e padrões de tratamento. O uso de trastuzumabe, associado ou não, foi custo-efetivo como tratamento de 1ª linha, diferentemente de quando usado como 2ª linha. Foram encontradas diferenças quanto à qualidade dos estudos incluídos. É necessária a realização de novas avaliações de custo-efetividade do trastuzumabe no câncer de mama metastático que, aliadas a fatores administrativos, sociais e políticos, embasem os gestores na tomada de decisão quanto à sua incorporação / Breast cancer is the type that affects more women worldwide. Approximately 30-50 % of patients diagnosed in the early stages will develop metastatic disease, which is considered incurable. At this stage of the disease, therapies aimed prolong survival and provide palliative symptom control. Trastuzumab, a monoclonal antibody targeted to the receptor of the human epidermal growth factor (HER2), has increased response rates, progression-free survival and/or overall survival in breast cancer and has recently been incorporated by the Sistema Único de Saúde (SUS) for treatment of early and locally advanced breast cancer. The aim of this study was to conduct a systematic review of the cost-effectiveness analyses of trastuzumab in patients with metastatic breast cancer overexpressing HER2. Searches were conducted between the period 1998-2013, on six electronic databases, two generic searches on the Internet, as well as manual search of references. We considered articles in English, Spanish and Portuguese, being excluded reviews, editorials, letters, case studies, review articles, systematic reviews and meta-analyses. The stages of study selection and data extraction were performed by two independent reviewers, and doubts were resolved by one third reviewer. Studies were assessed for quality according to approaches employed by Teerawattananon et al (2007). Data analysis was performed from the conversion of the costs and comments of the incremental cost-effectiveness ratios of trastuzumab were made. A quantity of 521 studies, all in English, was identified. Of these, we discarded 455 (294 did not meet the criteria for review and 161 duplicates). Sixty-six studies were included for reading the abstracts, resulting in 24 to read the full text. In total, 13 studies composed this review. The treatment regimens adopted on cost-effectiveness evaluations were varied. Eight studies compared the treatment of trastuzumab as 1st line for metastatic disease and five studies as 2nd line, which three of these used trastuzumab as comparator in the economic evaluation and not as an intervention. All studies using trastuzumab as 2nd line treatment did not consider it as a cost-effective intervention. Regarding the quality of the included studies, they showed a good quality, since most fulfilled the methodological guidelines for assessing costeffectiveness and used good evidence in the estimation of parameters. Finally, the evaluations used different thresholds to determine whether treatment with trastuzumab was cost-effective as well as differences in modeling costs, outcomes and treatment regimens. The use of trastuzumab, alone or associated, was cost-effective as treatment of 1st line, unlike when used as 2nd line. Differences were found in the quality of the included studies. Conducting new cost-effectiveness analyses of trastuzumab in metastatic breast cancer, allied to political, social and administrative factors, which helps decision makers about its incorporation, is required

Submitted by Biblioteca da Faculdade de Farmácia (bff@ndc.uff.br) on 2017-03-28T17:15:31Z No. of bitstreams: 1 Andrade, Thays Santos de [Dissertação, 2014].pdf: 467886 bytes, checksum: 9f9c6acd0d2516bb655fb10868b2db29 (MD5) / Made available in DSpace on 2017-03-28T17:15:31Z (GMT). No. of bitstreams: 1 Andrade, Thays Santos de [Dissertação, 2014].pdf: 467886 bytes, checksum: 9f9c6acd0d2516bb655fb10868b2db29 (MD5) / O câncer de mama é o tipo que mais acomete as mulheres em todo o mundo. Aproximadamente 30-50% dos pacientes diagnosticados nos estágios iniciais desenvolverão doença metastática, considerada incurável. Nesta fase da doença, as terapias objetivam prolongar a sobrevida e proporcionar controle paliativo dos sintomas. O trastuzumabe, um anticorpo monoclonal dirigido contra o receptor do fator de crescimento epidérmico humano (HER2), vem aumentando as taxas de respostas, sobrevida livre de progressão e/ou sobrevida global no câncer de mama, tendo sido recentemente incorporado pelo Sistema Único de Saúde (SUS) para tratamento de câncer de mama inicial e localmente avançado. O objetivo deste trabalho foi realizar uma revisão sistemática de avaliações de custo-efetividade do trastuzumabe em pacientes com câncer de mama metastático com superexpressão de HER2. Foram realizadas buscas, entre o período de 1998 a 2013, em seis bases de dados eletrônicas, duas ferramentas de busca na internet, além de pesquisa manual de referências. Foram considerados artigos em inglês, espanhol e português, sendo excluídos comentários, editoriais, cartas, estudos de caso, artigos de revisão, revisões sistemáticas e metanálises. As etapas de seleção dos estudos e extração dos dados foram realizadas por dois revisores independentes, e dúvidas foram resolvidas por um terceiro revisor. Os estudos foram avaliados em relação à qualidade seguindo abordagens empregadas por Teerawattananon et al. (2007). A análise dos dados foi realizada a partir da conversão dos custos e de observações das razões incrementais de custo-efetividade do trastuzumabe. Foram identificados 521 estudos, todos em inglês. Destes, descartou-se 455 (294 por não atenderem os critérios da revisão e 161 duplicatas). Sessenta e seis estudos foram incluídos para leitura dos resumos, resultando em 24 para leitura completa do texto. No total, 13 estudos compuseram esta revisão. Os esquemas terapêuticos adotados nas análises de custo-efetividade foram variados. Oito estudos compararam o tratamento do trastuzumabe como 1ª linha para doença metastática e cinco estudos como 2ª linha, sendo que três destes utilizaram o trastuzumabe como comparador na avaliação econômica e não como intervenção. Todos os estudos que utilizaram o trastuzumabe como 2ª linha de tratamento, não consideraram a intervenção custo-efetiva. Em relação à qualidade dos estudos incluídos, estes apresentaram uma boa qualidade, visto que a maioria cumpriu as diretrizes metodológicas de avaliação de custo-efetividade e utilizaram boas evidências na estimativa dos parâmetros. Finalmente, as análises utilizaram diferentes limiares para determinar se o tratamento com o trastuzumabe foi custo-efetivo, bem como diferenças na modelagem dos custos, desfechos e padrões de tratamento. O uso de trastuzumabe, associado ou não, foi custo-efetivo como tratamento de 1ª linha, diferentemente de quando usado como 2ª linha. Foram encontradas diferenças quanto à qualidade dos estudos incluídos. É necessária a realização de novas avaliações de custo-efetividade do trastuzumabe no câncer de mama metastático que, aliadas a fatores administrativos, sociais e políticos, embasem os gestores na tomada de decisão quanto à sua incorporação / Breast cancer is the type that affects more women worldwide. Approximately 30-50 % of patients diagnosed in the early stages will develop metastatic disease, which is considered incurable. At this stage of the disease, therapies aimed prolong survival and provide palliative symptom control. Trastuzumab, a monoclonal antibody targeted to the receptor of the human epidermal growth factor (HER2), has increased response rates, progression-free survival and/or overall survival in breast cancer and has recently been incorporated by the Sistema Único de Saúde (SUS) for treatment of early and locally advanced breast cancer. The aim of this study was to conduct a systematic review of the cost-effectiveness analyses of trastuzumab in patients with metastatic breast cancer overexpressing HER2. Searches were conducted between the period 1998-2013, on six electronic databases, two generic searches on the Internet, as well as manual search of references. We considered articles in English, Spanish and Portuguese, being excluded reviews, editorials, letters, case studies, review articles, systematic reviews and meta-analyses. The stages of study selection and data extraction were performed by two independent reviewers, and doubts were resolved by one third reviewer. Studies were assessed for quality according to approaches employed by Teerawattananon et al (2007). Data analysis was performed from the conversion of the costs and comments of the incremental cost-effectiveness ratios of trastuzumab were made. A quantity of 521 studies, all in English, was identified. Of these, we discarded 455 (294 did not meet the criteria for review and 161 duplicates). Sixty-six studies were included for reading the abstracts, resulting in 24 to read the full text. In total, 13 studies composed this review. The treatment regimens adopted on cost-effectiveness evaluations were varied. Eight studies compared the treatment of trastuzumab as 1st line for metastatic disease and five studies as 2nd line, which three of these used trastuzumab as comparator in the economic evaluation and not as an intervention. All studies using trastuzumab as 2nd line treatment did not consider it as a cost-effective intervention. Regarding the quality of the included studies, they showed a good quality, since most fulfilled the methodological guidelines for assessing costeffectiveness and used good evidence in the estimation of parameters. Finally, the evaluations used different thresholds to determine whether treatment with trastuzumab was cost-effective as well as differences in modeling costs, outcomes and treatment regimens. The use of trastuzumab, alone or associated, was cost-effective as treatment of 1st line, unlike when used as 2nd line. Differences were found in the quality of the included studies. Conducting new cost-effectiveness analyses of trastuzumab in metastatic breast cancer, allied to political, social and administrative factors, which helps decision makers about its incorporation, is required

Context. Agile methods address the challenges of an unpredictable world by relying on “people and their creativity rather than on processes”, accelerate delivery of software and considered as a reaction to plan-based or traditional methods. Distributed software development helps to access a pool of skilled personnel, completion of tasks around the clock and more. Incorporating of agile methods in distributed software development could help to solve some problems of distributed software development such as lack of communication and its dependencies, close collaboration and so on. Objectives. In this study we investigate the proposed benefits of pair programming, an XP development technique used by agile, and its effects on performance and social practices in distributed software development. Methods. Systematic literature review and an experiment are utilized to fulfill the objectives of this study. In the systematic review a sub-set of the research articles are selected relevant to the subject of this study from the electronic sources including, ACM Digital Library, IEEE, Xplore, EiVillage (Compendx, Inspec), Science Direct and ISI Web of Science. Experiment is conducted to investigate the pair programming effects on performance and social practices. Results. Many proposed benefits of pair programming in existing literature are identified and reported in both collocated and distributed settings. Pair programming is reported as an effective software development technique as well as a pedagogical tool. Experimental results showed that pair programming also effects performance in distributed software development, and positively impacts the social practices (human or social factors). Conclusions. There are many benefits of pair programming reported in collocated settings and less in distributed software development. Pair programming impacts the performance and social practices positively. However, we also conclude that the effective use of pair programming in distributed software development will yield the concrete results as well as the programmers’ pairs should be trained, experienced and well motivated for an effective use of pair programming and to overcome the challenges of distributed software development.

The Verification and Validation provides support to improve the quality of the software. Verification and Validation ensures that the product is stable and developed according to the requirements of the end user. This thesis presents a systematic review of dynamic programming languages and verification & validation practices used for dynamic languages. This thesis presents results found in dynamic programming languages and verification & validation over the period of 1985 – 2008. The study is aimed to start from identification of dynamic aspects along with the differences between static and dynamic languages. Furthermore, this thesis is also intends to give overview of the verification and validation practices for dynamic languages. Moreover to validate the verification and validation results, a survey consisting of (i) interviews and (ii) online survey is conducted. After the analysis of systematic review, it has been found that dynamic languages are making progress in some of the areas like integration of common development framework, language enhancement, dynamic aspects etc. The Dynamic languages are lacking in providing a better performance than static languages. There are also some factors found in this study that can raise the popularity of dynamic languages in the industry. Based on the analysis of systematic review, interviews and online survey, it is concluded that there is no difference between the methodologies available for Verification and Validation. It is also revealed that dynamic languages provide support to maintain software quality with their characteristics and dynamic features. Moreover, they also support to test softwares developed with static language. It is concluded that test driven development should be adopted while working with the dynamic languages. Test driven development is supposed to be a mandatory part of dynamic languages. / Farrakh Saeed +46765597558

Requirements traceability provides support for many software engineering activities like impact analysis, requirements validation and regression testing. In addition requirements traceability is the recognized component of many software process improvement initiatives. Requirements traceability also helps to control and manage evolution of a software system. This thesis presents a systematic review and a framework for requirements traceability. The systematic review is aimed at presenting fair evaluation of research concerning requirements traceability over the period 1997 – 2007. The systematic review aims at identifying probable gaps in research about requirements traceability and opens new horizons to explore. Moreover, two companies have been interviewed to understand the practice of requirements traceability in industry. After the analysis of industrial interviews these companies have been classified into two categories of traceability users. These categories are high-end traceability users and low-end traceability users. Based on the analysis of systematic review results and industrial interviews, this thesis presents a framework for requirements traceability called ‘Three Level Framework for Requirements Traceability (TLFRT)’. This framework is composed of three levels. The level 0 of this framework focuses on pre-RS traceability where as level 1 and level 2 focuses on post-RS traceability. The level 1 provide traceability for the functional requirements, where as level 2 provide traceability for non-functional requirements. TLFRT provides guidelines to a process that can be tailored to fit the needs of the high-end traceability users and low-end traceability users as well. This framework has been statically validated in two companies. The validation of TLFRT in industry resulted in compilation of lessons learned, which ensures that this theoretical framework could also be used in real industrial environment. The results of the research presented in this thesis are aimed at supporting requirements traceability by taking its current issues/challenges into account. / 0046(0)707381947

Objectives: The thesis comprises two parts. Firstly, a systematic review (SR) systematically examined meta-analytic studies assessing the prevalence of sexual abuse in childhood. A meta-analysis sought to systematically identify and synthesise data from studies providing prevalence estimates of contact and non-contact child sexual abuse (CSA) as self-reported by adolescents within the past 10 years. Methods: Consistent with Cochrane Collaboration guidelines, the systemic review adopted a comprehensive search of electronic databases and additional sources, including communication with authors working in the field, and the use of ancestry and descendency approaches between February 2013 and March 2014. The meta-analysis also adopted an equally systematic search conducted from March 2013 to June 2014. Assessment of quality and risk of bias were conducted on the included studies using PRISMA criteria and STROBE guidelines. Results: The systematic review identified six meta-analytic studies for review. The quality of studies and the range of definitional and methodological factors studied varied; results sections were well covered, whereas, quality and risk of bias within studies were generally poorly addressed. Prevalence estimates varied considerably and high heterogeneity was consistent across all analyses. Nine population studies measuring prevalence of contact and non-contact CSA were included in the meta-analysis. Meta-analyses were conducted overall and across male and female populations. Prevalence estimates varied considerably across studies, with contact CSA ranging from 2% to 39.8% and overall non-contact CSA, estimates ranged from 1% to 24.6%. Substantial heterogeneity was present across all analyses and therefore findings should be interpreted with caution. Nevertheless, the findings were thought-provoking and most likely due to differences in definitions of CSA and inconsistent use of validated instruments. Conclusions: Child sexual abuse is an international problem which is highly pervasive across all societies and populations studied. Females consistently report higher rates of CSA than males, and some Asian countries, namely China, produce relatively lower CSA estimates, even controlling for a wide range of methodological factors and study characteristics. The considerable heterogeneity was apparent both between and within studies and it appears likely based on the current findings, and in the context of previous research, that there are a wide range of methodological and socio-demographic factors which moderate CSA prevalence estimates. More specifically, the lack of a universally recognised definition of CSA proves especially problematic for researchers. The issue is further complicated by use of non-standardised instruments and inconsistent reporting and dissemination of findings. There is a need for future epidemiological studies to adhere to universal guidelines using standard definitions, standardisation of instruments and standardisation of reporting and dissemination to facilitate development of health policies, resource allocation and prevention initiatives for clinical and social services.

The aim of this thesis was to explore the relationships between the constructs of self-compassion (SC), self-esteem (SE) and recovery in psychosis. It is presented to the reader as three separate papers. 1) A systematic literature review exploring the relationships between SE and the positive symptoms of psychosis, 2) an empirical study investigating SC, SE, recovery in psychosis and positive psychotic symptoms and 3) a critical appraisal and personal reflection of the processes involved in conducting the research. Paper one presents a systematic review of the existing literature that explores the relationships between SE and the positive symptoms of psychosis. Thirty-four articles were identified which met the strict criteria. The evidence was mixed and much of it inconclusive. There was some support for the relationship between SE and delusions, in particular paranoia. The evidence for hallucinations was much less conclusive. Recommendations for future research were suggested as were potential clinical implications which arose from the review. The empirical study presented in paper two explores the relationships between SE, SC and recovery in psychosis, and aimed to assess whether SC was a unique predictor of recovery in psychosis, over and above the impact of SE (using cross-sectional and longitudinal analysis). Further exploratory analysis was conducted to ascertain whether specific positive symptoms of psychosis were related to SC and SE. At baseline, the results indicated that SC did not contribute unique variance in recovery from psychosis over and above that attributable to SE. Longitudinally, SC at baseline was not related to recovery at follow up. Exploratory analysis revealed levels of SE and SC were significantly different in groups who had a presence or absence hallucinations, but not delusions. Methodological strengths and limitations, clinical implications and ideas for future research discussed. Paper three provides the reader with a critical reflection of the processes involved in the undertaking of the two papers presented. Implications for clinical practice are discussed as well as directions for future research.

My own experiences of disjuncture sparked questions related to how practical nursing education is situated within the larger nursing disciplinary landscape. On acute care nursing units, work relationships are changing between RNs and LPNs as new collaborative care models are introduced, creating ambiguity and confusion with increasingly overlapping scopes of practice. Gaps remain in knowing how RNs and LPNs experience changes in these intra-professional team contexts, and how patient care, nursing work, and nursing education may be influenced by these new collaborative models. This has been the foundation for the journey towards graduate study and this dissertation work. In this dissertation I address the overarching research question: How are registered and practical nurses’ experiences of learning to work together being organized by educational and work contexts? This question consists of two sub-questions: 1) What are the experiences of pre-licensure health professional students and educators learning to work in intra-professional teams? and, 2) How are institutional texts organizing post-licensure nurses’ experiences of learning to practice on intra-professional teams? The first sub-question is addressed using the Joanna Briggs Institute (JBI) qualitative systematic review methodology to reveal what is currently known about how pre-licensure health professional students learn to work on intra-professional teams. The second question is approached using an institutional ethnographic analytic lens to explore how post-licensure nurses’ (RNs and LPNs) work is socially organized via educational, union, health authority, and regulatory texts and how this social organization impacts intra-professional relationships. Taking a plural approach to knowledge construction allows for a multi-perspectival view of RNs and LPNs experiences and the role of educational and work contexts in shaping how they learn to work together. Incorporating methodologies as diverse as a JBI systematic review and institutional ethnography raises methodological tensions. Each has its own philosophical assumptions, reflecting particular strengths and limitations in the production of knowledge. The challenges of employing a plural approach are explored alongside new knowledge and possibilities for exploring and understanding how best to care for patients and educate students within complex, collaborative environments. / Graduate / 2018-08-29

Objective: This work consisted of three research projects bridged by their focus on a multivariate assessment of executive functions in research and practice: (a) a systematic review and re-analysis of latent variable studies on executive function test batteries, (b) a confirmatory factor analysis (CFA) of the Delis-Kaplan Executive Function System (D-KEFS), the most commonly administered executive function test battery in clinical practice, and (c) the derivation of multivariate base rates for the D-KEFS, offering a psychometric resource with direct applications to clinical practice. Method: Systematic review. The systematic review identified 45 eligible samples (N=9,498 participants, mean age range: 3.01-74.40 years-old) and 21 correlation matrices eligible for re-analysis, comparing seven competing models including the most commonly evaluated factors: updating/working memory, inhibition, and shifting. Model results were summarized based on the mean percent accepted (i.e., mean rate at which models both properly converged and met fit thresholds: CFI≥.90/RMSEA≤.08). CFA. Using adults from the D-KEFS normative sample (N=425; 20-49 years-old), eight alternative measurement models were evaluated for a subset of D-KEFS tests. Factors from the accepted measurement model predicted three tests measuring constructs less often evaluated in the executive function literature: abstraction, reasoning, and problem solving. Base rates. The frequency of low scores occurring among the D-KEFS normative sample (N=1,050; 16-89 years-old) was calculated for the full D-KEFS and two brief batteries using stratifications for age, education, and intelligence. Results: Systematic review. The most often accepted models varied by age (preschool=one/two-factor; school-age=two/three-factor; adolescent/adult=three/nested-factor; older adult=two/three-factor), and most frequently included updating/working memory, inhibition, and shifting factors. The nested-factor and three-factor models were accepted most often and at similar rates among adult samples: 33-34% and 25-32%, respectively. No model was accepted most often for child/adolescent samples, but those with shifting differentiated garnered less support. CFA. A three-factor model including inhibition, shifting, and fluency fit the data well (CFI=0.938; RMSEA=0.047), although a two-factor model merging shifting/fluency fit similarly well (CFI=0.929; RMSEA=0.048). A bifactor model fit best (CFI=0.977; RMSEA=0.032), but rarely converged. Shifting best predicted tests of reasoning, abstraction, and problem solving (p<0.05; R2=0.246-0.408). Base rates. Low scores, based on commonly used clinical cutoffs, occurred frequently among healthy adults. For a three-test, four-test, and full D-KEFS battery, 62.8%, 71.8%, and 82.6% obtained ≥1 score(s) ≤16th percentile, respectively, and 36.1%, 42.0%, 50.7%, obtained ≥1 score(s) ≤5th percentile, respectively. The frequency of low scores increased with lower intelligence and fewer years of education. Discussion: The systematic review effort did not identify a definitive model of executive functions for either adults or children/adolescents, demonstrating the continued need to re-evaluate the conceptualization and measurement of this construct in future research. The D-KEFS CFA offers some evidence of clinical measures capturing theoretical constructs, but is not directly translatable into clinical practice; while the multivariate base rates are useful to clinicians, but do not bridge theory and assessment. This research reaffirms the elusive nature of executive functions in both research and clinical spheres, and represents a step forward in an enduring scientific process towards a true understanding of this mysterious construct. / Graduate / 2018-07-24

Ankylosing spondylitis (AS) is a chronic, inflammatory rheumatic disease that has a highly variable disease course. Three biologic agents, adalimumab, etanercept, and infliximab, have been developed for the treatment of AS. We conducted three studies: 1) an exploratory analysis of a year-long longitudinal dataset to gain insight into the variability of disease activity, physical function, and well-being and to explore the relationship between these outcome measures; 2) a systematic review of the available evidence for the efficacy of biologic treatment; 3) a systematic review of potential adverse effects of this treatment. We found that repeated measures of disease activity, function and well-being fluctuate considerably between patients, with complex patterns occurring over time within patients. There was mostly high quality evidence that these biologics are efficacious against placebo. We did not find evidence of an increase in serious adverse events or serious infections from short-term randomized controlled trials.