O objetivo desta investigação foi responder à seguinte questão: o que as escolas devem fazer para realizar completamente sua tarefa de formar leitores? Eu relatei e analisei os procedimentos do projeto Letras e Livros na cidade de Embu das Artes/SP, entre os anos 2002 e 2006, que produziram uma redução substancial do número de crianças não alfabetizadas após quatro anos de escola. Os efeitos positivos desta ação fortaleceram nossa suposição, de que o apoio individual para crianças, social e cognitivamente vulneráveis, foi efetivo. Eles confirmaram também a hipótese de base psicogenética do valor das consignas de interesse pessoal e leitura cooperativa. A ampliação do repertório literário através de leitura em voz alta também foi decisiva. Os estudos de caso, produzidos durante o projeto, usados para análise e como modelo inspiradores no processo de formação, mostraram-se úteis para o aperfeiçoamento profissional da equipe. / The main purpose of this investigation was to answer the following question: what must schools do to fulfill completely their task of forming readers? I have related and analysed the procedures of the project Letras e Livros in the city of Embu das Artes/SP during the years 2002 to 2006, which produced a substantial reduction in the number of children who were not able read after four years of school. Positive effects of these actions suport our assumption, that individual personalysed help offered to socially and cognitinely vulnerable children were effective. They suported also the psychogenetically based hypothesis of the value of personally significant tasks and cooperative reading. Enlarging literary konowledge through oral readings was decisive too.The best case reports produced during the project were used for analysis and inspiring model prooving useful to improvement of professional skills.

The use of multimodal communication by one moderately mentally retarded, nonphysically impaired teenage girl was investigated. Eighty minutes of language samples were transcribed, coded, and analysed for modes of communication, communicative intent, discourse function, and context of conversation. It was found that six different modes of communication, and various combinations of these modes, were used throughout the samples. A strong relationship between mode of communication and communicative Intent was found. Furthermore, the context of conversation influenced the mode of communication. No strong relationship was found, however, between discourse function and mode of communication. Implications of this research for a theory of multimodal communication in the nonverbal, as well as suggestions for clinical intervention with this population, are discussed. / Medicine, Faculty of / Audiology and Speech Sciences, School of / Graduate

In this work I deal with the question of whether the use of the concept of overdetermination is coherent across 1) psychoanalytic theoretical and case studies and 2) different psychoanalytic directions. Based on the analysis of the most cited case studies dealing with the topic of narcissism in the field of Kleinian and Relational psychoanalysis, I come to the conclusion that the use of the concept of overdetermination is not completely coherent in psychoanalysis. This incoherence may be due to the different attitudes of different authors to abstract metapsychological assumptions. Narcissism of small differences, which in my opinion is evident between representatives of different psychoanalytic directions, can also play a role. And last but not least, it is possible to look at this incoherence as the result of so-called implicit theories, i.e. not entirely official and conscious theories that psychoanalysts follow in the course of their practical clinical work. Keywords Psychoanalytic discourse, overdetermination, analysis of psychotherapeutic case reports, the relationship between theory and practice ;

Based on the definition and assessment methods proposed in Chapter 2, an analysis of accuracy at the phonetic, spelling, lexical, syntactic, semantic, and textual levels is given, together with an examination of the impact of extra-linguistic factors, such as the time and place of translation, initiator's policy, and translators. The last section defines the texts for the present study. / Chapter 1 is a review of the literature on translation quality assessment in China and in the West. / Chapter 2 reviews the study of accuracy in scientific and technical translation, including an introduction to accuracy, research on accuracy, and definition of accuracy, which involves completeness in information transfer, consistency in terminology, grammaticality in the encoding of the target text, and methods of assessing linguistic accuracy. / Chapter 3 proposes a new theoretical framework and presents texts for the study of accuracy. Apart from complete transfer of information, consistency in terminology, and grammaticality in the encoding of the target text, accuracy should also be assessed by the function of the target text and the impact of extra-linguistic factors. / Chapter 4 is a contrastive analysis of the source and target texts on the basis of the above theoretical framework. This analysis includes features of the source and target texts, methods in translating terms in traditional Chinese medicine, methods in assessing semantic accuracy, types of Chinese medicine formulas and their methods of translation, types of errors in the target texts, and the impact of extra-linguistic factors on translation. / Chapter 5 discusses methods of assessing accuracy with the use of computer-aided tools, illustrating them with examples and offering explanations on the terms and statistics. The software used are Wordsmith 3.0 (Scott, 1998) and MonoConc Pro 2.0 (Barlow, 2000). / Chapter 6 examines computer-aided assessment of the translation of The Pharmacopoeia with a more comprehensive error analysis of the target texts. It is shown that compared with human analysis, computer analysis has a higher speed in search, a broader range of texts, a faster production of wordlists, and a faster and better calculation of errors. This is a more comprehensive assessment of translation accuracy. It concludes with an analysis of the possible impact of the extra-linguistic factors on linguistic encoding. / Chapter 7 proposes methods to improve accuracy through the construction of the bilingual term bank, and offers suggestions to improve the translation by the construction of a translation memory with the computer-aided tools provided by Trados. A comparison of the new translations with the old ones shows marked improvements in the former. / Chapter 8 concludes with the major findings in this thesis. Firstly, computer-aided assessment of accuracy in scientific and technical translation is faster and broader than human assessment. Secondly, methods for assessing accuracy with computer-aided tools are important in filling up gaps in human assessment. Lastly, computer-aided accuracy assessment has a great impact on other relevant areas. / In scientific and technical translation, accuracy is most important. However, the operative aspect of accuracy assessment still eludes us. This is a thorny issue in translation studies and practice. / The purpose of the present study is to use computer tools, such as Wordsmith 3.0 (Scott, 1998) and MonoConc Pro 2.0 (Barlow, 2000), to help to assess accuracy in the English translation of Chinese pharmacological writings, a specific area of scientific and technical translation. The texts used for this study have been selected from the bilingual versions of The Pharmacopoeia of the People's Republic of China (Beijing: Chemical Industry Press, 2000; The Pharmacopoeia hereafter). / The theoretical framework adopted in this thesis is the translation quality assessment model proposed by Reiss (1971/2000) and Vermeer (1996). The emphasis is on the definition and assessment of "accuracy" so as to provide an operative method to assess accuracy in translation, which is supplemented by a computer-aided approach to accuracy. This is done in the following ways: (1) The creation of a bilingual term bank of 1,500 entries and a translation corpus based on the source texts, target texts and 8 Chinese-English dictionaries of medicine. (2) The categorization of the formula names and linguistic items in the source texts and the definition of accuracy and its assessment methods based on research findings in scientific and technical translation. (3) The quantitative and qualitative analysis of translation errors based on the above definition and methods. (4) The comparison of new translations, produced with the aid of computer tools, with the old ones to demonstrate the validity and applicability of the new approach to accuracy assessment. / This thesis is divided into 8 chapters. / 錢多秀. / 呈交日期: 2005年12月. / 論文(哲學博士)--香港中文大學, 2006. / 參考文獻(p. 198-211). / Cheng jiao ri qi: 2005 nian 12 yue. / Adviser: Sin-Wai Chan. / Source: Dissertation Abstracts International, Volume: 67-11, Section: A, page: 4165. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in Chinese and English. / School code: 1307. / Lun wen (zhe xue bo shi)--Xianggang Zhong wen da xue, 2006. / Can kao wen xian (p. 198-211). / Qian Duoxiu.

Background: The rapid diffusion of Novel Psychoactive Substances (NPS) constitutes an important challenge in terms of public health and a novelty in clinical settings, where these compounds may lead to erratic symptoms, unascertained effects and multi-intoxication scenarios, especially in emergency situations. The number of NPS available on the illicit drug market is astonishing: official reports suggest the appearance of a new drug every week. NPS may be enlisted in many different families such as synthetic phenethylamines, tryptamines, cathinones, piperazines, ketamine-like compounds, cannabimimetics and other plant-derived, medical products and derivatives. Therefore, healthcare services and professionals are often called to face this unknown 'galaxy' where NPS users seem to perceive traditional services 'unfitting' for their needs, requiring an attention which is quite different from known classic drug abusers. In this context, the Recreational Drugs European Network (ReDNet), a research project funded the European Commission and led by the University of Hertfordshire, aimed to explore the NPS galaxy and develop information tools for vulnerable individuals and professionals working with them. This initiative reported specific Technical Folders on new drugs and disseminated the collected information through innovative communication technologies (e.g. multimedia tools, social networking and mobile phone services) internationally. Aim and objectives: The aim of this work is to evaluate and contribute to expand the knowledge of health professionals on NPS. The key objectives are: 1) to assess the level of knowledge on NPS amongst a sample of Italian healthcare professionals; 2) to evaluate the effectiveness of dissemination tools developed by ReDNet, including an SMS-Email/mobile service (SMAIL); 3) to understand the clinical impact of NPS by providing four Technical Folders and collecting two clinical cases on NPS. Methodology: According to the objectives, the methodological approach has been articulated in the following three phases. Phase 1: investigating knowledge and preferred channels of information via an online survey among health professionals in Italy. This first Italian study on NPS awareness had been online from February to July 2011, recruiting participants from Departments of Addiction, Psychiatry and other services. Phase 2: evaluating the ReDNet initiative. An evaluation questionnaire was designed and disseminated online to assess the various resources provided by ReDNet project; it had been online from April to July 2013, targeting professionals registered to ReDNet services. This phase also investigated the SMAIL service, a mobile application that was the latest technological tool developed by ReDNet team. Phase 3: promoting evidence based work in clinical practice through the preparation of four Technical Folders and two case reports. Technical Folders followed the methodology optimised during the ReDNet experience, organising NPS data under specific headings, measured for the need of health professionals. Case reports were collected in a Dual Diagnosis Unit in Italy ('Casa di Cura Parco dei Tigli'); assessed patients revealed for the first time the use of NPS; clinical interviews were conducted to collect a full anamnesis while for the first time psychopathological characteristics were measured in NPS abusers, using a psychometric instrument (MMPI-2). Results: In Phase 1 Italian services, in particular interviewees (n=243) from Departments of Psychiatry and Addiction, showed a strong interest for the subject but a poor understanding of NPS: 26.7% of respondents did not know if their patients ever used NPS; at the same time they considered this phenomenon as very relevant to their profession (e.g. psychomotor agitation [75.7%], errors in the assessment [75.7%], management of the clients [72%]); in addition less of a quarter of them had reliable information on new substances. Interviewees also reported the need for easily accessible channels of information to expand their expertise in the field (including emails [70%] and dedicated websites [51.9%]). The ReDNet initiative (Phase 2) reached professionals (n=270) from European countries and various other regions; they appreciated the website above all (48.5%), which provided access to other information (in form of academic papers, news, technical folders, etc.). The integration of technological-based and classic educational resources was used to self-educate professionals (52.6%) and supply information for research (33.7%) with up-to-date and 3 reliable information; in the same Phase the SMAIL service was analysed in its first 557 searches: in the pilot period 122 professionals used SMS inquiries (95%), asking information on NPS while highlighting the increasing number of NPS available on the market. Technical folders (Phase 3) described two new phenethylamines (Bromo-dragonfly and 25I-NBOMe), a novel ethno drug (Kratom) and a new synthetic cathinone (alpha-PVP) whose severe effects were also described in one of the clinical cases. The first case report (Alice) involved a clubber who used mephedrone and other NPS with a severe worsening of her psychiatric disturbances; the second one (Marvin) described a patient who was referred by a psychiatric service and revealed himself as a 'psychonaut' with an intense abuse of alpha-PVP. Conclusions: The exploration of the NPS galaxy is a new challenge for healthcare professionals. In this study, Italian services seemed to be unprepared to face the emergency and requested rapid access to reliable information; the ReDNet project provided both technology-based and traditional resources to expand knowledge on NPS, making professionals more aware of emerging issues and helping especially clinicians working in the field (e.g. via SMAIL service and Technical Folders). Overall, it can be observed that effective information services on NPS targeted at professionals initiatives should include an online interface integrating up-to-date information, describing NPS through specific Technical Folders and disseminating scientific literature; the use of technological tools, including mobile applications, is an important strategy to support health professionals in their activity. Finally, more 'visual' guidelines, possibly in the form of a 'map' of these heterogeneous compounds, could be a useful framework to describe NPS to physicians and other professionals who are often unprepared and unconfident to face such an expanding galaxy.

Introdução: Na fase pré-comercialização, os ensaios clínicos randomizados (ECRs) constituem-se em ferramenta primordial no acúmulo de informação sobre a segurança de um medicamento. Recomendações têm sido publicadas no sentido de que a informação sobre eventos adversos seja adequadamente descrita nesses estudos. Na fase pós-comercialização, vigilância ativa e passiva complementam-se e relatos de caso de reações adversas a medicamentos (RAMs) publicados em revistas médicas deveriam contribuir no processo de geração de sinal, alertando o meio científico e auxiliando na adoção de medidas pelas agências regulatórias de medicamentos. Seu impacto, no entanto, é incerto, seja na geração de estudos confirmatórios ou incorporação das RAMs em fontes de informação sobre medicamentos utilizadas na prática médica. Objetivo: avaliar, em revistas de alto impacto da área médica: 1) a adoção das recomendações da versão do CONSORT “Better Reporting of Harms in Randomized Trials: An Extension of the CONSORT Statement” e das recomendações propostas por outros autores em ECRs envolvendo medicamentos publicados em 2009; 2) o impacto de relatos de caso de RAMs novas publicados em 1998, através da geração de estudos controlados confirmatórios e inclusão na base de dados MICROMEDEX e no British National Formulary (BNF). Metodologia: Através de buscas no Medline, foram selecionados todos os ECRs envolvendo medicamentos publicados em 2009 nas revistas British Medical Journal, The Journal of The American Medical Association, The Lancet e The New England Journal of Medicine e os relatos de caso publicados em 1998 nas revistas Annals of Internal Medicine, Archives of Internal Medicine, The Journal of the American Medical Association e New England Journal of Medicine. Baseando-se nas recomendações propostas por Ioannidis e Lau e na versão ampliada do CONSORT, as informações sobre eventos adversos foram extraídas dos ECRs. O impacto dos relatos de caso foi avaliado através da geração de estudos controlados confirmatórios publicados em revistas indexadas no Medline e/ou EMBASE e da incorporação da informação na base de dados MICROMEDEX e no BNF. Resultados: Dos 122 ECRs analisados, 32,8% objetivaram avaliar desfechos de segurança do medicamento em questão (posicionando-se a este respeito na introdução), 72,1% mencionaram riscos no título ou resumo; 10,7% esclareceram como a informação sobre riscos foi coletada; 46,7% apresentaram as frequências dos eventos adversos, separando-os por tipo e braço do estudo e especificando se algum tipo de evento adverso não ocorreu; e 18,0% apresentaram discussão balanceada sobre riscos e benefícios. Dos 32 relatos de caso de RAMs novas avaliados, verificou-se a inclusão da RAM em questão no MICROMEDEX em 16 (50%) relatos de caso e, no BNF, em 10 (32,1%). Observou-se geração de estudos controlados confirmatórios para 4 (12,5%) relatos. Conclusões: Informações importantes sobre eventos adversos permanecem insuficientemente atendidas em ECRs. Relatos de caso publicados em revistas médicas desempenham papel importante no processo de geração de sinal, impactando relativamente na geração de estudos confirmatórios e em fontes de informação da prática médica. / Introduction: In pre-commercialization phase, randomized clinical trials (RCTs) represent an essential tool for obtaining information on drug safety. Recommendations have been published so that the information about adverse events is properly described in these studies. In the pre-commercialization phase, active and passive vigilance complement one another, and case reports of adverse reactions to drugs (ADRs) published in medical journals should contribute for the process of sign generation, making the scientific world alert and supporting the adoption of measures by the regulatory drug agencies. Its impact, nonetheless, remains uncertain, both regarding the generation of confirmation studies and the ADR acceptance in the drug information sources used in the medical practice. This study aims at assessing, in highly-impacting medical journals: the compliance with the recommendations from the CONSORT version ‘Better Reporting of Harms in Randomized Trials: An Extension of the CONSORT Statement’ , as well as with the ones proposed by other authors in RCTs involving drugs, published in 2009; the impact of new ADR case reports published in 1998, through carrying out controlled confirmation studies and including them in the MICROMEDEX databank and in the British National Formulary (BNF). Methodology: Through Medline search, all the RCTs involving drugs published in 2009 in the journals British Medical Journal, The Journal of The American Medical Association, The Lancet and The New England Journal of Medicine were chosen. The same was done for the case reports published in 1998 in the Annals of Internal Medicine, Archives of Internal Medicine, The Journal of the American Medical Association and New England Journal of Medicine. Based on the recommendations proposed by Ioannidis and Lau and in the CONSORT comprehensive version, the information on adverse events was extracted from the RCTs. The impact of the case reports was assessed through carrying out controlled confirmation studies published in journals indexed in the Medline and/or EMBASE and the inclusion of this information in the MICROMEDEX databank and the BNF. Outcomes: Among the 122 RCTs analyzed, 72.1% mentioned risks in the title or abstract; 10.7% explained how information on risks had been collected; 46.7% presented adverse event frequency, sorting them by kind and study ramification, and also specifying whether some kind of adverse event had not occurred; and 18.0% presented a balanced discussion on risks and benefits. Among the 32 new ADR case reports analyzed, it was verified that these ADRs were included in the MICROMEDEX in 16 (50%) of the case reports, and in the BNF in 10 (32.1%). It was observed that controlled confirmation studies were designed for 4 (12.5%) of these studies. Conclusions: Relevant information on adverse events remains insufficient in RCTs. Case reports published in medical journals play an important part in the sign generating process, and they also relatively impact the carrying out of confirmation studies and the information sources of the medical practice.

Background: Vestibular function (specifically, horizontal semicircular canal function) can be assessed across a broad frequency range using several different techniques. The head impulse test is a qualitative test of horizontal semicircular canal function that can be completed at bedside. Recently, a new instrument (video head impulse test [vHIT]) has been developed to provide an objective assessment to the clinical test. Questions persist regarding how this test may be used in the overall vestibular test battery. Purpose: The purpose of this case report is to describe vestibular test results (vHIT, rotational testing, vestibular evoked myogenic potentials, and balance and gait performance) in an individual with a 100% unilateral caloric weakness who was asymptomatic for dizziness, vertigo or imbalance. Data Collection and/or Analysis: Comprehensive assessment was completed to evaluate vestibular function. Caloric irrigations, rotary chair testing, vHIT, and vestibular evoked myogenic potentials were completed. Results: A 100% left-sided unilateral caloric weakness was observed in an asymptomatic individual. vHIT produced normal gain with covert saccades. Conclusions: This case demonstrates the clinical usefulness of vHIT as a diagnostic tool and indicator of vestibular compensation and functional status.

Introdução: Na fase pré-comercialização, os ensaios clínicos randomizados (ECRs) constituem-se em ferramenta primordial no acúmulo de informação sobre a segurança de um medicamento. Recomendações têm sido publicadas no sentido de que a informação sobre eventos adversos seja adequadamente descrita nesses estudos. Na fase pós-comercialização, vigilância ativa e passiva complementam-se e relatos de caso de reações adversas a medicamentos (RAMs) publicados em revistas médicas deveriam contribuir no processo de geração de sinal, alertando o meio científico e auxiliando na adoção de medidas pelas agências regulatórias de medicamentos. Seu impacto, no entanto, é incerto, seja na geração de estudos confirmatórios ou incorporação das RAMs em fontes de informação sobre medicamentos utilizadas na prática médica. Objetivo: avaliar, em revistas de alto impacto da área médica: 1) a adoção das recomendações da versão do CONSORT “Better Reporting of Harms in Randomized Trials: An Extension of the CONSORT Statement” e das recomendações propostas por outros autores em ECRs envolvendo medicamentos publicados em 2009; 2) o impacto de relatos de caso de RAMs novas publicados em 1998, através da geração de estudos controlados confirmatórios e inclusão na base de dados MICROMEDEX e no British National Formulary (BNF). Metodologia: Através de buscas no Medline, foram selecionados todos os ECRs envolvendo medicamentos publicados em 2009 nas revistas British Medical Journal, The Journal of The American Medical Association, The Lancet e The New England Journal of Medicine e os relatos de caso publicados em 1998 nas revistas Annals of Internal Medicine, Archives of Internal Medicine, The Journal of the American Medical Association e New England Journal of Medicine. Baseando-se nas recomendações propostas por Ioannidis e Lau e na versão ampliada do CONSORT, as informações sobre eventos adversos foram extraídas dos ECRs. O impacto dos relatos de caso foi avaliado através da geração de estudos controlados confirmatórios publicados em revistas indexadas no Medline e/ou EMBASE e da incorporação da informação na base de dados MICROMEDEX e no BNF. Resultados: Dos 122 ECRs analisados, 32,8% objetivaram avaliar desfechos de segurança do medicamento em questão (posicionando-se a este respeito na introdução), 72,1% mencionaram riscos no título ou resumo; 10,7% esclareceram como a informação sobre riscos foi coletada; 46,7% apresentaram as frequências dos eventos adversos, separando-os por tipo e braço do estudo e especificando se algum tipo de evento adverso não ocorreu; e 18,0% apresentaram discussão balanceada sobre riscos e benefícios. Dos 32 relatos de caso de RAMs novas avaliados, verificou-se a inclusão da RAM em questão no MICROMEDEX em 16 (50%) relatos de caso e, no BNF, em 10 (32,1%). Observou-se geração de estudos controlados confirmatórios para 4 (12,5%) relatos. Conclusões: Informações importantes sobre eventos adversos permanecem insuficientemente atendidas em ECRs. Relatos de caso publicados em revistas médicas desempenham papel importante no processo de geração de sinal, impactando relativamente na geração de estudos confirmatórios e em fontes de informação da prática médica. / Introduction: In pre-commercialization phase, randomized clinical trials (RCTs) represent an essential tool for obtaining information on drug safety. Recommendations have been published so that the information about adverse events is properly described in these studies. In the pre-commercialization phase, active and passive vigilance complement one another, and case reports of adverse reactions to drugs (ADRs) published in medical journals should contribute for the process of sign generation, making the scientific world alert and supporting the adoption of measures by the regulatory drug agencies. Its impact, nonetheless, remains uncertain, both regarding the generation of confirmation studies and the ADR acceptance in the drug information sources used in the medical practice. This study aims at assessing, in highly-impacting medical journals: the compliance with the recommendations from the CONSORT version ‘Better Reporting of Harms in Randomized Trials: An Extension of the CONSORT Statement’ , as well as with the ones proposed by other authors in RCTs involving drugs, published in 2009; the impact of new ADR case reports published in 1998, through carrying out controlled confirmation studies and including them in the MICROMEDEX databank and in the British National Formulary (BNF). Methodology: Through Medline search, all the RCTs involving drugs published in 2009 in the journals British Medical Journal, The Journal of The American Medical Association, The Lancet and The New England Journal of Medicine were chosen. The same was done for the case reports published in 1998 in the Annals of Internal Medicine, Archives of Internal Medicine, The Journal of the American Medical Association and New England Journal of Medicine. Based on the recommendations proposed by Ioannidis and Lau and in the CONSORT comprehensive version, the information on adverse events was extracted from the RCTs. The impact of the case reports was assessed through carrying out controlled confirmation studies published in journals indexed in the Medline and/or EMBASE and the inclusion of this information in the MICROMEDEX databank and the BNF. Outcomes: Among the 122 RCTs analyzed, 72.1% mentioned risks in the title or abstract; 10.7% explained how information on risks had been collected; 46.7% presented adverse event frequency, sorting them by kind and study ramification, and also specifying whether some kind of adverse event had not occurred; and 18.0% presented a balanced discussion on risks and benefits. Among the 32 new ADR case reports analyzed, it was verified that these ADRs were included in the MICROMEDEX in 16 (50%) of the case reports, and in the BNF in 10 (32.1%). It was observed that controlled confirmation studies were designed for 4 (12.5%) of these studies. Conclusions: Relevant information on adverse events remains insufficient in RCTs. Case reports published in medical journals play an important part in the sign generating process, and they also relatively impact the carrying out of confirmation studies and the information sources of the medical practice.

Introdução: Na fase pré-comercialização, os ensaios clínicos randomizados (ECRs) constituem-se em ferramenta primordial no acúmulo de informação sobre a segurança de um medicamento. Recomendações têm sido publicadas no sentido de que a informação sobre eventos adversos seja adequadamente descrita nesses estudos. Na fase pós-comercialização, vigilância ativa e passiva complementam-se e relatos de caso de reações adversas a medicamentos (RAMs) publicados em revistas médicas deveriam contribuir no processo de geração de sinal, alertando o meio científico e auxiliando na adoção de medidas pelas agências regulatórias de medicamentos. Seu impacto, no entanto, é incerto, seja na geração de estudos confirmatórios ou incorporação das RAMs em fontes de informação sobre medicamentos utilizadas na prática médica. Objetivo: avaliar, em revistas de alto impacto da área médica: 1) a adoção das recomendações da versão do CONSORT “Better Reporting of Harms in Randomized Trials: An Extension of the CONSORT Statement” e das recomendações propostas por outros autores em ECRs envolvendo medicamentos publicados em 2009; 2) o impacto de relatos de caso de RAMs novas publicados em 1998, através da geração de estudos controlados confirmatórios e inclusão na base de dados MICROMEDEX e no British National Formulary (BNF). Metodologia: Através de buscas no Medline, foram selecionados todos os ECRs envolvendo medicamentos publicados em 2009 nas revistas British Medical Journal, The Journal of The American Medical Association, The Lancet e The New England Journal of Medicine e os relatos de caso publicados em 1998 nas revistas Annals of Internal Medicine, Archives of Internal Medicine, The Journal of the American Medical Association e New England Journal of Medicine. Baseando-se nas recomendações propostas por Ioannidis e Lau e na versão ampliada do CONSORT, as informações sobre eventos adversos foram extraídas dos ECRs. O impacto dos relatos de caso foi avaliado através da geração de estudos controlados confirmatórios publicados em revistas indexadas no Medline e/ou EMBASE e da incorporação da informação na base de dados MICROMEDEX e no BNF. Resultados: Dos 122 ECRs analisados, 32,8% objetivaram avaliar desfechos de segurança do medicamento em questão (posicionando-se a este respeito na introdução), 72,1% mencionaram riscos no título ou resumo; 10,7% esclareceram como a informação sobre riscos foi coletada; 46,7% apresentaram as frequências dos eventos adversos, separando-os por tipo e braço do estudo e especificando se algum tipo de evento adverso não ocorreu; e 18,0% apresentaram discussão balanceada sobre riscos e benefícios. Dos 32 relatos de caso de RAMs novas avaliados, verificou-se a inclusão da RAM em questão no MICROMEDEX em 16 (50%) relatos de caso e, no BNF, em 10 (32,1%). Observou-se geração de estudos controlados confirmatórios para 4 (12,5%) relatos. Conclusões: Informações importantes sobre eventos adversos permanecem insuficientemente atendidas em ECRs. Relatos de caso publicados em revistas médicas desempenham papel importante no processo de geração de sinal, impactando relativamente na geração de estudos confirmatórios e em fontes de informação da prática médica. / Introduction: In pre-commercialization phase, randomized clinical trials (RCTs) represent an essential tool for obtaining information on drug safety. Recommendations have been published so that the information about adverse events is properly described in these studies. In the pre-commercialization phase, active and passive vigilance complement one another, and case reports of adverse reactions to drugs (ADRs) published in medical journals should contribute for the process of sign generation, making the scientific world alert and supporting the adoption of measures by the regulatory drug agencies. Its impact, nonetheless, remains uncertain, both regarding the generation of confirmation studies and the ADR acceptance in the drug information sources used in the medical practice. This study aims at assessing, in highly-impacting medical journals: the compliance with the recommendations from the CONSORT version ‘Better Reporting of Harms in Randomized Trials: An Extension of the CONSORT Statement’ , as well as with the ones proposed by other authors in RCTs involving drugs, published in 2009; the impact of new ADR case reports published in 1998, through carrying out controlled confirmation studies and including them in the MICROMEDEX databank and in the British National Formulary (BNF). Methodology: Through Medline search, all the RCTs involving drugs published in 2009 in the journals British Medical Journal, The Journal of The American Medical Association, The Lancet and The New England Journal of Medicine were chosen. The same was done for the case reports published in 1998 in the Annals of Internal Medicine, Archives of Internal Medicine, The Journal of the American Medical Association and New England Journal of Medicine. Based on the recommendations proposed by Ioannidis and Lau and in the CONSORT comprehensive version, the information on adverse events was extracted from the RCTs. The impact of the case reports was assessed through carrying out controlled confirmation studies published in journals indexed in the Medline and/or EMBASE and the inclusion of this information in the MICROMEDEX databank and the BNF. Outcomes: Among the 122 RCTs analyzed, 72.1% mentioned risks in the title or abstract; 10.7% explained how information on risks had been collected; 46.7% presented adverse event frequency, sorting them by kind and study ramification, and also specifying whether some kind of adverse event had not occurred; and 18.0% presented a balanced discussion on risks and benefits. Among the 32 new ADR case reports analyzed, it was verified that these ADRs were included in the MICROMEDEX in 16 (50%) of the case reports, and in the BNF in 10 (32.1%). It was observed that controlled confirmation studies were designed for 4 (12.5%) of these studies. Conclusions: Relevant information on adverse events remains insufficient in RCTs. Case reports published in medical journals play an important part in the sign generating process, and they also relatively impact the carrying out of confirmation studies and the information sources of the medical practice.

Clinical observations of individual patients are the cornerstones for furthering our understanding of the human body, diseases, and therapeutics. Traditionally, clinical observations were communicated through publishing case reports and case series. The effort of identifying and investigating unusual clinical observations has always rested on the shoulders of busy clinicians. To date, there has been little effort dedicated to increasing the efficiency of identifying unique and uncommon patient observations that may lead to valuable discoveries. In this thesis, we propose and implement an augmented intelligence framework to identify potential novel clinical observations by combining machine analytics through outlier analysis with the judgment of subject-matter experts. Preeclampsia is a significant cause of maternal and perinatal mortality and morbidity, and advances in its management have been slow. Considering the complex etiological nature of preeclampsia, clinical observations are essential in advancing our understanding of the disease and therapeutic approaches. Thus, the objectives and studies in this thesis aim to answer the hypothesis that using outlier analysis in preeclampsia-related medical data would lead to identifying previously uninvestigated clinical cases with new clinical insight. This thesis combines three articles published or submitted for publication in peer-reviewed journals. The first article (published) is a systematic review examining the extent to which case reports and case series in preeclampsia have contributed new knowledge or discoveries. We report that under one-third of the identified case reports and case series presented new knowledge. In our second article (submitted for publication), we provide an overview of outlier analysis and introduce the framework of augmented intelligence using our proposed extreme misclassification contextual outlier analysis approach. Furthermore, we conduct a systematic review of obstetrics-related research that used outlier analysis to answer scientific questions. Our systematic review findings indicate that such use is in its infancy. In our third article (published), we implement the proposed augmented intelligence framework using two different outlier analysis methods on two independent datasets from separate studies in preeclampsia and hypertensive disorders of pregnancy. We identify several clinical observations as potential novelties, thus supporting the feasibility and applicability of outlier analysis to accelerate clinical discovery.