京都大学 / 新制・課程博士 / 博士(医学) / 甲第23756号 / 医博第4802号 / 新制||医||1056(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 中山 健夫, 教授 村井 俊哉, 教授 小杉 眞司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Purpose The objective of this thesis is to establish an evidence-based clinical practice guideline for the primary management of obstetrical brachial plexus injury (OBPI). Four gaps are identified for management of OBPI in Canada: 1) The historic poor use of evidence, 2) Timing of referral to multidisciplinary care, 3) Indications and timing of operative nerve repair, and 4) Distribution of expertise in Canada. Methods The guideline is intended for all providers delivering perinatal care, and all specialists delivering care to OBPI patients. The consensus group was composed of clinicians representing each of Canada’s ten multidisciplinary centres. An original systematic review comparing the effectiveness of primary operative versus nonoperative management, and a review of Canadian OBPI epidemiology were completed. Quality indicators for referral to a multidisciplinary centre were established. Recommendations were based on best evidence, and interpretation of this evidence by clinical experts. An electronic modified Delphi approach was used for consensus, with agreement criteria defined a priori following RAND procedures. Results Nerve repair reduces functional impairment in OBPI versus nonoperative management of similar patients, and modern microsurgery has low incidence of major adverse events. The quality of evidence was low. Residual impairment is underestimated and uncharacterized in nonoperative literature. OBPI incidence was at least 1.24 per 1000 births in Canada, and consistent over the study period. The strongest risk factors for OBPI were comorbid humerus fracture, shoulder dystocia and comorbid clavicle fracture. Most patients were not referred to a multidisciplinary centre. The guideline group approved seven recommendations. Discussion Recommendations address the identified gaps in care, and guide identification, referral, treatment and outcome assessment for OBPI. The process established a new network of opinion leaders and researchers for further guideline development, and multicentre research. The next step is to facilitate the implementation of the recommendations. / Thesis / Master of Science (MSc)

Suite aux notifications de cas de comportements suicidaires associés aux antidépresseurs (ADs) chez les jeunes, une mise en garde réglementaire a été émise en mai 2004 au Canada, et deux guides de pratique clinique ont été publiés dans la littérature en novembre 2007. L'objectif de ce mémoire fut d'évaluer l’association entre ces interventions de communication et le suivi médical de la population pédiatrique traitée par ADs au Québec. Une étude de cohorte rétrospective (1998-2008) a été menée chez 4 576 enfants (10-14 ans) et 12 419 adolescents (15-19 ans) membres du régime public d’assurance médicaments du Québec, ayant débuté un traitement par AD. Le suivi médical dans les trois premiers mois de traitement a été mesuré par l’occurrence et la fréquence de visites médicales retrouvées dans les banques de données de la RAMQ. Les facteurs associés à un suivi conforme aux recommandations ont été évalués à partir de modèles de régression logistique multivariés. Seuls 20% des enfants ou adolescents ont eu au moins une visite de suivi à chaque mois, en conformité avec les recommandations. La probabilité de recevoir un suivi médical conforme était plus élevée lorsque le prescripteur initial était un psychiatre. L’occurrence et la fréquence des visites n’ont pas changé après la publication de la mise en garde ou des recommandations. De ce mémoire on conclut que d'autres interventions visant à optimiser le suivi médical devraient être envisagées. / Following reports of a potential association between antidepressants (ADs) and suicidal behaviour in youth, a regulatory warning was issued in Canada in May 2004, and clinical practice guidelines on recommended medical follow-up were published in the literature in November 2007. This Master's thesis aimed at assessing the association between these communication interventions and medical follow-up practices. A retrospective cohort study (1998-2008) was conducted among 4,576 children (10-14 years) and 12,419 adolescents (15-19 years) members of the Quebec public drug plan. Medical follow-up was ascertained through patterns of physician billing practices found in the RAMQ medical services databases. Study outcomes consisted of occurrence and frequency of visits in the first three months of AD treatment. Factors associated with follow-up consistent with recommendations were identified through multivariate logistic regression models. The main independent variable was exposure to each of the communication interventions. Covariates included: gender, class of AD, number of concomitant chronic diseases, psychiatric conditions, prescriber’s specialty, and potential exposure to each intervention. Only 20% of children or adolescents received at least one visit each month. The probability of receiving adequate follow-up was greater when treatment was initiated by a psychiatrist. Occurrence and frequency of visits did not change after the warning nor the publication of the recommendations. From this thesis, one may conclude that further interventions to optimize medical follow-up practices should be envisaged.

Suspeita-se da Síndrome de Lynch (SL) a partir da história pessoal e familial do indivíduo. Posteriormente, os dados histopatológicos, imuno-histoquímicos e moleculares podem ser utilizados para aprimorar o diagnóstico da doença. Entretanto, um grande desafio no diagnóstico da Síndrome de Lynch é a baixa acurácia dos critérios clínicos utilizados. OBJETIVOS: Avaliar a frequência de SL em pacientes submetidos a tratamento cirúrgico por câncer colorretal e com história familial de câncer. Avaliar quais dos critérios clínicos e/ou moleculares seriam mais informativos no diagnóstico desta Síndrome na população brasileira. PACIENTES E MÉTODOS: Estudaram-se 458 casos de câncer colorretal (CCR), do Serviço de Coloproctologia do Departamento de Gastroenterologia do Hospital das Clínicas - FMUSP, de janeiro de 2005 a dezembro de 2008. História familial (HF) positiva para CCR ocorreu em 118 pacientes. Promoveu-se a revisão das lâminas para critérios histopatológicos de MSI (diretrizes de Bethesda), avaliação imuno-histoquímica (IHC) para as proteínas MLH1, MSH2, MSH6, PMS2, através do complexo avidina-biotina-peroxidase e instabilidade de microssatélites (MSI) (BAT-25, BAT-26, NR-21, NR-24 e MONO-27). Realizada a análise da mutação somática para o BRAF em todos os casos com MSI positiva. RESULTADOS: Dos 118 pacientes com HF, 61 (51,69%) preencheram pelo menos um dos critérios de Bethesda revisados. 36 eram do sexo feminino (59%), média de idade de 53,2 anos. Nove (14,7%) pacientes apresentaram todos os critérios de Amsterdam I. Cinquenta e dois tumores localizaram-se no cólon esquerdo. Os componentes histopatológicos de MSI incluíram: linfócitos intratumoral (47,5%), característica expansiva do tumor (29,5%) e o componente mucinoso (27,8%) (componentes histopatológicos de MSI instável) em 44 (72%). A IHC estava alterada em oito (13%) e a MSI em 12 pacientes (20%). Houve associação entre os critérios de Amsterdam I e MSI e na IHC com MLH1 e PMS2. Houve associação entre os critérios de Bethesda revisados com o sexo, na histopatologia com o componente mucinoso e a reação Crohn like; com a MSI e na IHC com o MLH1 e PMS2. O BRAF foi realizado nos 12 casos com MSI positiva e em todos os casos foram negativos. Os indivíduos que apresentaram o critério 4 de Bethesda revisado (CCR ou câncer associado a SL, diagnosticado em um ou mais parentes de primeiro grau, desde que uma das neoplasias tenha ocorrido antes dos 50 anos de idade), tiveram uma chance 10,6 vezes maior de apresentar MSI positiva. Propôs-se um escore para caracterizar pacientes com SL baseado nas variáveis estudadas nesta pesquisa. CONCLUSÕES: A frequência de Síndrome de Lynch nos pacientes submetidos a ressecção por câncer e com história familial foi de 20%. O critério 4 de Bethesda revisado associou-se mais fortemente à presença de instabilidade de microssatélites na população estudada. O escore desenvolvido neste estudo contribui como uma ferramenta prática na ampliação diagnóstica da Síndrome de Lynch / Lynch Syndrome is suspected due to the personal and familial history of the individual. Subsequently, histopathological, immunohistochemical and molecular data can be used to improve diagnosis of the disease. However, a major challenge in the diagnosis of Lynch Syndrome is the low accuracy of clinical criteria. OBJECTIVES: To assess the frequency of Lynch Syndrome in patients with familial cancer history submitted to colorectal cancer resection. To assess what clinical and / or molecular criteria would be the most informative in the diagnosis of this syndrome in Brazilian population. PATIENTS AND METHODS: 458 colorectal cancer (CRC) cases were studied, from the Coloproctology Unit of the Department of Gastroenterology, Hospital das Clinicas - USP, from January 2005 to December 2008. Positive family history (FH) for CRC occurred in 118 patients. The pathologic slides were reviewed for histological criteria for MSI (Bethesda guidelines), immunohistochemical analysis (IHC) for MLH1, MSH2, MSH6, PMS2 proteins, through the avidin-biotin-peroxidase complex, and microsatellite instability (MSI) (BAT-25, BAT-26, NR-21, NR-24 and MONO-27). BRAF somatic mutation was analyzed in all cases with positive MSI. RESULTS: Of the 118 patients with HF, 61 (51.69%) met at least one of the revised Bethesda criteria. Thirty-six were female (59%), and the mean age was 53.2 years. Nine (14.7%) patients presented all Amsterdam criteria I. Fifty-two tumors were located in the left colon. MSI histopathological components included: intratumoral lymphocytes (47.5%), expansive characteristics of the tumor (29.5%) and mucinous component (27.8%) (Histological unstable components of MSI) in 44 (72%). IHC was abnormal in eight (13%) and MSI in 12 patients (20%). There was an association between the Amsterdam criteria I and MSI; and between IHC with MLH1 and PMS2. There was an association with the revised Bethesda criteria with: sex, mucinous histology and Crohn\'s like reaction; with MSI and IHC with PMS2 and MLH1. BRAF was performed in 12 patients with MSI positive, and all were negative. Patients who presented the revised Bethesda criteria 4 (CRC or cancer associated with SL, diagnosed in one or more first-degree relatives, with one of the neoplasms occurred before 50 years of age), had a 10.6 increased chance to display positive MSI. Based on the studied variables, we proposed a score to characterize the Lynch Syndrome. CONCLUSIONS: The frequence of Lynch Syndrome in patients who were submitted to cancer resection, and had a cancer familial history was 20%. The criterion 4 Revised Bethesda was associated more strongly with the presence of microsatellite instability in the studied population. The developed score contributes as a practical tool in the diagnosis of Lynch Syndrome

Submitted by Maicon Juliano Schmidt (maicons) on 2015-07-10T18:45:36Z No. of bitstreams: 1 Thiago da Silva.pdf: 1419570 bytes, checksum: 6c6e9d3e986eb659ac40f20394e683f6 (MD5) / Made available in DSpace on 2015-07-10T18:45:36Z (GMT). No. of bitstreams: 1 Thiago da Silva.pdf: 1419570 bytes, checksum: 6c6e9d3e986eb659ac40f20394e683f6 (MD5) Previous issue date: 2014-07-04 / Nenhuma / OBJETIVO: identificar e analisar as melhores evidências cientifica como suporte teórico para a elaboração de um protocolo assistencial para o manejo da dor de pacientes adultos cirúrgicos. METODOLOGIA: trata-se de estudo exploratório, realizado em bases de dados através dos descritores obtidos no MeSH/Decs: Acute pain; chronic pain; General surgery; Analgesics; Clinical protocols; Practice guideline; Pain measurement; Pain; Post-Surgery; Post-Operative. A busca foi realizada nas bases de dados PubMed, LILACS e COCHRANE, utilizando-se o método PICO, compreendendo artigos escritos em inglês ou português, a partir de 2001 e classificados conforme o sistema de classificação de Nível de Evidência do Oxford Center for Evidence Based Medicine e o grau de recomendação e o nível de evidência no enfoque tratamento, prevenção, etiologia e diagnóstico, do Grading of Recommendations Assessment, Development and Evaluation ? GRADE. Todos os direitos autorais foram preservados. RESULTADOS: dos 424 artigos encontrados, 29 foram selecionados. Identificaram-se evidências quanto à classificação da intensidade da dor conforme o tipo de cirurgia, os instrumentos para sua avaliação e os principais agentes farmacológicos para o seu manejo. Os resultados mostraram que a maioria dos artigos são do Brasil e Estados Unidos, sendo a maior produção em 2013 (8 artigos), 2009 (5 artigos) e 2010 (4 artigos). As melhores evidências encontradas foram 16 ensaios clínicos randomizado e seis revisões sistemáticas de ensaios clínicos randomizado. A escala de mensuração da dor mais utilizada é a Escala Visual Analógica. Deve ser classificada conforme sua intensidade e seu manejo deve ser adequado de acordo com a potência do analgésico prescrito. CONCLUSÃO: os estudos identificaram inúmeras fragilidades, não existindo um planejamento farmacológico adequado ao paciente cirúrgico. A criação deste protocolo propiciou um caminho seguro e uma base científica de qualidade para o manejo da dor e vêm ao encontro das diretrizes estabelecidas pela Agência Americana de Pesquisa e Qualidade em Saúde Pública, e a Sociedade Americana da Dor. / OBJECTIVE: to identify and analyze the best scientific evidence and theoretical support for the development of a protocol assistance for pain management of surgical adult patients. METHODOLOGY: this is an exploratory study conducted in databases obtained through the descriptors in MeSH / Decs: Acute pain; chronic pain; General surgery; Analgesics; Clinical protocols; Practice guideline; Pain measurement; Pain; Post-Surgery; Post-Operative. The search was performed in PubMed, LILACS and COCHRANE data, using the PICO method, comprising articles written in English or Portuguese, from 2001 and classified according to the classification system LoE of the Oxford Centre for Evidence Based Medicine and grade of recommendation and level of evidence approach in treatment, prevention, etiology and diagnosis, the Grading of Recommendations Assessment, Development and Evaluation - GRADE. All copyrights are preserved. RESULTS: among the 424 articles found, 29 were selected. We identified evidence for the classification of pain intensity according to the type of surgery, the instruments for their assessment and the main pharmacologic agents for its management. The results showed that most of the articles are from Brazil and the United States, with the largest production in 2013 (8 articles), 2009 (5 items) and 2010 (4 articles). The best evidence found were 16 randomized clinical trials and systematic reviews of six randomized clinical trials. The measurement scale is the most widely used pain Visual Analog Scale. Should be classified according to their intensity and their management should be appropriate according to the prescribed analgesic potency. CONCLUSION: the studies identified numerous weaknesses, with no adequate pharmacological planning to surgical patients. The creation of this protocol provided a safe journey and a scientific basis for quality pain management and come to meet the guidelines established by the American Agency for Research and Quality in Public Health, and the American Pain Society.

Suspeita-se da Síndrome de Lynch (SL) a partir da história pessoal e familial do indivíduo. Posteriormente, os dados histopatológicos, imuno-histoquímicos e moleculares podem ser utilizados para aprimorar o diagnóstico da doença. Entretanto, um grande desafio no diagnóstico da Síndrome de Lynch é a baixa acurácia dos critérios clínicos utilizados. OBJETIVOS: Avaliar a frequência de SL em pacientes submetidos a tratamento cirúrgico por câncer colorretal e com história familial de câncer. Avaliar quais dos critérios clínicos e/ou moleculares seriam mais informativos no diagnóstico desta Síndrome na população brasileira. PACIENTES E MÉTODOS: Estudaram-se 458 casos de câncer colorretal (CCR), do Serviço de Coloproctologia do Departamento de Gastroenterologia do Hospital das Clínicas - FMUSP, de janeiro de 2005 a dezembro de 2008. História familial (HF) positiva para CCR ocorreu em 118 pacientes. Promoveu-se a revisão das lâminas para critérios histopatológicos de MSI (diretrizes de Bethesda), avaliação imuno-histoquímica (IHC) para as proteínas MLH1, MSH2, MSH6, PMS2, através do complexo avidina-biotina-peroxidase e instabilidade de microssatélites (MSI) (BAT-25, BAT-26, NR-21, NR-24 e MONO-27). Realizada a análise da mutação somática para o BRAF em todos os casos com MSI positiva. RESULTADOS: Dos 118 pacientes com HF, 61 (51,69%) preencheram pelo menos um dos critérios de Bethesda revisados. 36 eram do sexo feminino (59%), média de idade de 53,2 anos. Nove (14,7%) pacientes apresentaram todos os critérios de Amsterdam I. Cinquenta e dois tumores localizaram-se no cólon esquerdo. Os componentes histopatológicos de MSI incluíram: linfócitos intratumoral (47,5%), característica expansiva do tumor (29,5%) e o componente mucinoso (27,8%) (componentes histopatológicos de MSI instável) em 44 (72%). A IHC estava alterada em oito (13%) e a MSI em 12 pacientes (20%). Houve associação entre os critérios de Amsterdam I e MSI e na IHC com MLH1 e PMS2. Houve associação entre os critérios de Bethesda revisados com o sexo, na histopatologia com o componente mucinoso e a reação Crohn like; com a MSI e na IHC com o MLH1 e PMS2. O BRAF foi realizado nos 12 casos com MSI positiva e em todos os casos foram negativos. Os indivíduos que apresentaram o critério 4 de Bethesda revisado (CCR ou câncer associado a SL, diagnosticado em um ou mais parentes de primeiro grau, desde que uma das neoplasias tenha ocorrido antes dos 50 anos de idade), tiveram uma chance 10,6 vezes maior de apresentar MSI positiva. Propôs-se um escore para caracterizar pacientes com SL baseado nas variáveis estudadas nesta pesquisa. CONCLUSÕES: A frequência de Síndrome de Lynch nos pacientes submetidos a ressecção por câncer e com história familial foi de 20%. O critério 4 de Bethesda revisado associou-se mais fortemente à presença de instabilidade de microssatélites na população estudada. O escore desenvolvido neste estudo contribui como uma ferramenta prática na ampliação diagnóstica da Síndrome de Lynch / Lynch Syndrome is suspected due to the personal and familial history of the individual. Subsequently, histopathological, immunohistochemical and molecular data can be used to improve diagnosis of the disease. However, a major challenge in the diagnosis of Lynch Syndrome is the low accuracy of clinical criteria. OBJECTIVES: To assess the frequency of Lynch Syndrome in patients with familial cancer history submitted to colorectal cancer resection. To assess what clinical and / or molecular criteria would be the most informative in the diagnosis of this syndrome in Brazilian population. PATIENTS AND METHODS: 458 colorectal cancer (CRC) cases were studied, from the Coloproctology Unit of the Department of Gastroenterology, Hospital das Clinicas - USP, from January 2005 to December 2008. Positive family history (FH) for CRC occurred in 118 patients. The pathologic slides were reviewed for histological criteria for MSI (Bethesda guidelines), immunohistochemical analysis (IHC) for MLH1, MSH2, MSH6, PMS2 proteins, through the avidin-biotin-peroxidase complex, and microsatellite instability (MSI) (BAT-25, BAT-26, NR-21, NR-24 and MONO-27). BRAF somatic mutation was analyzed in all cases with positive MSI. RESULTS: Of the 118 patients with HF, 61 (51.69%) met at least one of the revised Bethesda criteria. Thirty-six were female (59%), and the mean age was 53.2 years. Nine (14.7%) patients presented all Amsterdam criteria I. Fifty-two tumors were located in the left colon. MSI histopathological components included: intratumoral lymphocytes (47.5%), expansive characteristics of the tumor (29.5%) and mucinous component (27.8%) (Histological unstable components of MSI) in 44 (72%). IHC was abnormal in eight (13%) and MSI in 12 patients (20%). There was an association between the Amsterdam criteria I and MSI; and between IHC with MLH1 and PMS2. There was an association with the revised Bethesda criteria with: sex, mucinous histology and Crohn\'s like reaction; with MSI and IHC with PMS2 and MLH1. BRAF was performed in 12 patients with MSI positive, and all were negative. Patients who presented the revised Bethesda criteria 4 (CRC or cancer associated with SL, diagnosed in one or more first-degree relatives, with one of the neoplasms occurred before 50 years of age), had a 10.6 increased chance to display positive MSI. Based on the studied variables, we proposed a score to characterize the Lynch Syndrome. CONCLUSIONS: The frequence of Lynch Syndrome in patients who were submitted to cancer resection, and had a cancer familial history was 20%. The criterion 4 Revised Bethesda was associated more strongly with the presence of microsatellite instability in the studied population. The developed score contributes as a practical tool in the diagnosis of Lynch Syndrome

Demensvården i Sverige och i andra delar av världen har på olika sätt varit i fokus de senaste åren där man påtalat behovet att utveckla metoder och riktlinjer för hur vården ska bedrivas. Detta för att möta den växande andelen äldre människor som också utvecklar demenssjukdomar. Nationella projekt har drivits, företrädesvis i syfte att förbättra vård och omsorg av personer med demenssjukdom, men även för att förbättra diagnosticering och behandling. I denna avhandling beskrivs utvecklingen av det dator-baserade beslutsstödet för demensutredning, DMSS (Dementia Management and Support System), som syftar till att fungera som ett stöd för personer som arbetar med att diagnosticera och behandla personer med kognitiv sjukdom. Domänen valdes även på grund av dess komplicerade kunskapsinnehåll, där bland annat en spännvidd av olika typer av symptom, komplexa kliniska mätmetoder sett ur ett formaliseringsperspektiv, starkt teamorienterat arbetssätt, ställer krav på hur kunskap ska och är möjlig att formaliseras och integreras i ett beslutsstödsystem för att det ska bli användbart i kliniskt arbete. De olika studierna och delprojekten som beskrivs i avhandlingen syftar till att tillsammans skapa en grund för utveckling av ett kliniskt kognitivt verktyg som stödjer och utvecklar användarens kognitiva processer (lärande, beslutsfattande, resonemang, etc.), samtidigt som det stödjer utvecklingen av det kliniska arbetet vari systemet ingår. I detta arbete fokuseras demensutredning som applikationsomr åde. Analyser har gjorts av den vidare användarkontexten, resonemangsprocesser, domän- och processkunskapen uttryckt i evidensbaserad litteratur och integrerad i klinisk praktik, terminologier samt formaliseringstekniker som kan hantera domänkunskapens egenskaper och användarsituationens krav. Prototyper har utvecklats och utvärderats i en iterativ process i samarbete med domänexperter, för användande i klinisk praktik i Sverige och Japan. För dessa studier har kvalitativa metoder använts i syfte att fånga så många olika aspekter som möjligt angående formalisering och interaktion, samt av praktiska skäl då det funnits begränsad tillgång till expertanvändare och patienter. Triangulering av metoder har tillämpats för att validera resultat. Kliniska utredningsverksamheter är komplexa processer, som är situerade, emergenta och styrda av individens behov, men även begränsade eller möjliggjorda av tillgängliga resurser på olika vårdnivåer i vårdprocessen. Det behövs metoder och verktyg som kan användas vid utveckling av system som syftar till att stödja dessa verksamheter. Det finns exempel på metoder som utvecklats för transformation av informell klinisk kunskap till en formell struktur som kan implementeras i ett beslutsstödsystem, där verktyg har utvecklats primärt i syfte att hjälpa kliniska experter att transformera sin kunskap till något en systemutvecklare kan använda. Den största nackdelen med dessa angreppssätt är att de är tidskrävande för experterna att sätta sej in i och använda. En metod har tillämpats i detta arbete där en teoribildning, som är gemensam för flera forskningsområden, använts för att strukturera klinisk process- och domänkunskap i en form som kan användas i formaliseringsarbete. Den konceptuella modellen av kliniskt arbete som utvecklats är baserad på verksamhetsteorin, kompletterad med general logics som kategoriskt, formellt teoretiskt ramverk för att möjliggöra transformationer mellan olika logiska språk och flexibel representation av riktlinjer och kunskap. Genom att göra en grundlig verksamhetsanalys utifrån ett aktivitetsperspektiv med hjälp av modellen, kan komponenter identifieras som kan formaliseras i en kunskapsbas och/eller kompletteras genom en design och implementation av ett gränssnitt som stödjer ett interaktivt resonemang och den kliniska processen. Resultatet av verkamhetsanalys och andra studier som presenteras i denna avhandling kommer att ligga till grund för vidare utveckling av DMSS för olika användarmiljöer, till att börja med i Sverige och Japan. Extensioner av systemet kommer att utvecklas som stödjer de olika ingående professionerna på olika vårdnivåer. Den konceptuella modellen kommer att utvecklas och tillämpas i framtida utvecklingsprojekt där beslutsstöd är en central komponent. Det formella ramverket kommer att utvecklas i syfte att kunna analysera och förfina kunskap i perspektivet av exempelvis olika set av kliniska riktlinjer som ställer olika krav på komplexitet hos logiken. Stödet till ett interaktivt resonemang vid användandet av systemet ska utvecklas med en kunskapsbas och ett dynamiskt gränssnitt speciellt utformat för ändamålet. Hittills har i första hand kvalitativa aspekter och syften varit i fokus i de olika projekten. Därför behöver varje utvecklingslinje ytterligare utvecklas med kvantitativa mål. Utvidgade utvärderingsstudier pågår, som syftar till att undersöka fördelning mellan olika nivåer av komplexitet hos patienter och vilken typ av stöd som behövs för respektive. När systemet är integrerat i daglig verksamhet kan faktorer som hur användande av systemet påverkar användaren och verksamheten undersökas. / There is a need to improve dementia care in Sweden. The main issues discussed are how to improve the competence of medical personnel and the quality of diagnosis and intervention. In this thesis the process of developing a decision-support system for the investigation of dementia is described, as one means to meet the need. The resulting prototype system DMSS (Dementia Management Support System) has been developed in cooperation with domain experts, and has been evaluated and redesigned in the process in an iterative development process. The process involves the assessment of evidence-based domain knowledge and its characteristics, the assessment of the procedural knowledge residing in clinical practice, and reasoning processes. Further, the terminology and main reasoning process integrated in the system have been validated. Qualitative methods have been used for these parts of the project for the purpose of assessing as many different aspects as possible, and for practical reasons due to the limited access to domain experts, patients and primary care physicians in the area. Triangulation of methods has been applied in order to validate results in the process. The development has been extended to also include prototypes for Japanese clinical environments. Clinical investigation activities are complex processes, which are situated, emergent and directed by the individual need of the patient, but also restricted or enhanced by the available resources at different points and at different care levels in the process. For the purpose of creating a system which provides support throughout the investigation process, the domain knowledge and the clinical investigation process was analysed and formalised in a conceptual model of clinical activity, developed based on activity theory and case studies of patients. The need for methods for the transformation of informal results from field studies into formal knowledge and design is addressed by providing the framework, which integrates the conceptual model of clinical activity and a method for the assessment and transformation of the knowledge to be integrated in a decision-support system. The model was used to identify actions and their characteristics suitable for formalisation in a decision-support system. Several sources of domain knowledge need to be integrated that express the knowledge differently, which increases the demands on a formalism for representation. The work towards formalising the diagnostic reasoning process in both typical and atypical patient's cases is presented, where the evidence in ambiguous cases is valued within different frames of references in order to improve specificity. Different logical frameworks have been applied, evaluated and developed using case studies of patients. Two lines of work towards a dementia logic and flexible guideline representation is presented; the defeasible, non-monotonic approach where many-valued dictionaries are used in a context-based argumentation framework; and the monotonic approach of integrating reasoning in a fundamental view of transformations between logics, using general logics as generalised and categorical framework.

Suite aux notifications de cas de comportements suicidaires associés aux antidépresseurs (ADs) chez les jeunes, une mise en garde réglementaire a été émise en mai 2004 au Canada, et deux guides de pratique clinique ont été publiés dans la littérature en novembre 2007. L'objectif de ce mémoire fut d'évaluer l’association entre ces interventions de communication et le suivi médical de la population pédiatrique traitée par ADs au Québec. Une étude de cohorte rétrospective (1998-2008) a été menée chez 4 576 enfants (10-14 ans) et 12 419 adolescents (15-19 ans) membres du régime public d’assurance médicaments du Québec, ayant débuté un traitement par AD. Le suivi médical dans les trois premiers mois de traitement a été mesuré par l’occurrence et la fréquence de visites médicales retrouvées dans les banques de données de la RAMQ. Les facteurs associés à un suivi conforme aux recommandations ont été évalués à partir de modèles de régression logistique multivariés. Seuls 20% des enfants ou adolescents ont eu au moins une visite de suivi à chaque mois, en conformité avec les recommandations. La probabilité de recevoir un suivi médical conforme était plus élevée lorsque le prescripteur initial était un psychiatre. L’occurrence et la fréquence des visites n’ont pas changé après la publication de la mise en garde ou des recommandations. De ce mémoire on conclut que d'autres interventions visant à optimiser le suivi médical devraient être envisagées. / Following reports of a potential association between antidepressants (ADs) and suicidal behaviour in youth, a regulatory warning was issued in Canada in May 2004, and clinical practice guidelines on recommended medical follow-up were published in the literature in November 2007. This Master's thesis aimed at assessing the association between these communication interventions and medical follow-up practices. A retrospective cohort study (1998-2008) was conducted among 4,576 children (10-14 years) and 12,419 adolescents (15-19 years) members of the Quebec public drug plan. Medical follow-up was ascertained through patterns of physician billing practices found in the RAMQ medical services databases. Study outcomes consisted of occurrence and frequency of visits in the first three months of AD treatment. Factors associated with follow-up consistent with recommendations were identified through multivariate logistic regression models. The main independent variable was exposure to each of the communication interventions. Covariates included: gender, class of AD, number of concomitant chronic diseases, psychiatric conditions, prescriber’s specialty, and potential exposure to each intervention. Only 20% of children or adolescents received at least one visit each month. The probability of receiving adequate follow-up was greater when treatment was initiated by a psychiatrist. Occurrence and frequency of visits did not change after the warning nor the publication of the recommendations. From this thesis, one may conclude that further interventions to optimize medical follow-up practices should be envisaged.

Ständige Weiterentwicklungen von Behandlungsmöglichkeiten, die Technisierung der Medizin und die Liberalisierung des Gesundheitssystems führen auf Seiten der Versorger zu vermehrten Anstrengungen, die eigenen Geschäftsprozesse in Klinischen Pfaden zu dokumentieren, um auf dieser Basis eine medizinische und betriebswirtschaftliche Optimierung durchzuführen. Für die Entwicklung Klinischer Pfade ist die Einbeziehung Medizinischer Leitlinien unablässig, da sie für definierte Symptomkomplexe den aktuellen Stand der Forschung aggregieren. Gleichwohl sind sie Schulungsunterlagen, direkte Entscheidungshilfen oder Aufklärungsdokumente für Patienten und damit keinesfalls ausschließlich auf die Entwicklung Klinischer Pfade ausgerichtet. Dadurch geht die Leitlinien-getriebene Entwicklung Klinischer Pfade mit einem hohen interpretativen Aufwand auf Seiten der Anwender einher. Aus der Motivation diesen Prozess methodisch zu unterstützen, leitet sich die zentrale Forschungsfrage der Arbeit ab: Wie kann eine Methode gestaltet sein, die eine zielgerichtete Ableitung von Klinischen Pfaden aus Medizinischen Leitlinien zulässt? Dieser Frage nimmt sich die vorliegende Arbeit an und präsentiert einen referenzmodellbasierten Ansatz, diese bestehende methodische Lücke zu schließen. Das Lösungsartefakt setzt dabei direkt auf Seiten der Medizinischen Leitlinie an. Die Methode, kurz MAC, besteht aus drei Methodenfragmenten: dem Rollenmodell, in welchem die Aufgabenträgertypen und ihre Verantwortlichkeiten beschrieben werden, dem Produktfragment, welches den Entwurf einer Modellierungssprache zur Kodierung von Medizinischen Leitlinien und deren Wiederverwendung in Klinischen Pfaden auf Basis einer Referenzmodelladaption vorsieht, und dem Vorgehensmodell, in dem Handlungsanweisungen für die zuvor beschriebenen Aufgabenträgertypen spezifiziert sind. Die Arbeit leistet damit einen Beitrag zum Methodenspektrum der Wirtschaftsinformatik. Forschungsmethodisch ordnet sich die Arbeit in die gestaltungsorientierte Artefaktforschung (Design Science) ein.:Teil A - Zusammenfassung Abbildungsverzeichnis Tabellenverzeichnis Abkürzungsverzeichnis 0 Einleitung 0.1 Hintergrund 0.2 Gegenstand und Motivation 0.3 Forschungsdesign 0.3.1 Wissenschaftstheoretische Positionierung 0.3.2 Forschungsziel 0.3.3 Forschungsmethode 1 Aufbau der Arbeit 1.1 Publikation P1: Konzeptuelle Modellierung im klinischen Umfeld 1.2 Publikation P2: Reference Modeling in Health Care – State-of-the-art and Proposal for the Construction and Application of a Reference Model 1.3 Publikation P3: From Clinical Practice Guideline to Clinical Pathway – Issues of Reference Model-Based Approach 1.4 Publikation P4: Anforderungen an eine Methode zur Ableitung Klinischer Pfade aus Medizinischen Leitlinien 1.5 Publikation P5: Methode zur Ableitung Klinischer Pfade aus Medizinischen Leitlinien 2 Fazit 2.1 Beitrag der Arbeit 2.2 Kritische Würdigung und weiterer Forschungsbedarf Literaturverzeichnis Anhang A Teil B - Einzelpublikationen

<p><strong>Introduction:</strong> In Ontario alone, an estimated 6,700 people (3,000 women; 3,700 men) will die of lung cancer in 2011 (Canadian Cancer Society, 2011). A diagnosis of cancer is associated with complex decisions; the array of choices of cancer treatments brings about hope, but also anxiety over which treatment is best suited for the individual patient (Blank, Graves, Sepucha et al., 2006). The overall cancer experience depends on the quality of this decision (Blank et al., 2006). Clinical practice guidelines are knowledge translation tools to facilitate treatment decision-making. In Ontario, guidelines have been developed and disseminated with the purpose to inform clinical decisions, improve evidence based practice, and to reduce unwanted practice variation in the province. But has this been achieved? To study this issue, the purpose of the current study was to gain an in-depth understanding and develop a theoretical framework of how Ontario physicians are making treatment decisions with their non-small cell lung cancer patients. The following research questions guided the study: (a) How do physicians make treatment decisions with their stage II, stage IIIA and stage IIIB non-small cell lung cancer patients in Ontario? (b) How do knowledge translation tools, such as Cancer Care Ontario guidelines, influence the decision-making process?</p> <p><strong>Methods:</strong> A qualitative approach of grounded theory, following a social constructivist paradigm outlined by Kathy Charmaz (2006), was used in this study. 21 semi-structured interviews were conducted; 16 interviews with physicians and 5 with health care administrators. The method of analysis integrated grounded theory philosophy to identify the treatment decision-making process in non-small cell lung cancer, from the physician perspective.</p> <p><strong>Findings:</strong> The theory depicts the treatment decision-making process to involve five key “guides” (or factors) to inform the treatment-decision making process: the unique patient, the unique physician, the family, the clinical team, and the clinical evidence.</p> <p><strong>Conclusion:</strong> Decision-making roles in lung cancer are complex and nuanced. The use of evidence, such as, clinical practice guidelines, is one of many considerations. Information from a large number of sources and a wide array of factors, people, emotions, preferences, clinical expertise, experiences, and clinical evidence informs the dynamic process of treatment decision-making. This theory of the treatment decision-making process (from the physician perspective) has implications relevant to treatment decision-making research, theory development, and guideline development for non-small cell lung cancer.</p> / Master of Science (MSc)