京都大学 / 新制・課程博士 / 博士(医学) / 甲第23798号 / 医博第4844号 / 新制||医||1058(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 佐藤 俊哉, 教授 黒田 知宏, 教授 永井 洋士 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

ABSTRACT Background: For patients with life-limiting illnesses, having adequate knowledge of prognosis can strongly impact the choice between curative and supportive treatment. Objectives: The purpose of this research study is to explore patient understanding of prognosis and to illuminate the experience of having or not having prognostic information in people diagnosed with life-limiting illnesses. This study aims to investigate the patient's understanding of the term "prognosis", the significance of the term "prognosis" to the patient, and how prognosis may or may not affect future treatment choices. In addition, this study aims to further understand the experience of prognostic communication between provider and patient. The over-arching goal is to capture the personal perspectives of participants with a view to exploring their experiences around knowledge of their prognosis. Methods: A qualitative research design using a phenomenological approach was employed to examine how people experience prognosis. An invitation to participate in the study was publically announced via local newspapers, social media venues, and word of mouth. Participants who responded to study advertisements and who met inclusion criteria were asked to participate in one interview answering open-ended questions aimed at examining their experience with and knowledge of their prognosis. In addition, questions about prognostic communication between patient and health care provider were explored. All interviews were recorded, transcribed verbatim and analyzed using phenomenological methods. Results: Three study participants met the study criteria and were interviewed. Several themes emerged from the data including 1) patients have need for information about their illness, 2) prognostic data inform treatment choices, 3) patient experiences are unique and 4) patients feel a connection to nurses involved in their care. Conclusions: This study illuminated the patients' desire and need for information during their illness, the desire for patient autonomy, the difficulty of starting and having prognostic conversations, the downstream impact of having prognostic information, and the important role that nurses play for patients facing serious health issues. It is hopeful that the themes identified during the course of this research ultimately contribute to the knowledge base by informing healthcare providers on the importance of conveying prognostic information in a timely, direct, and sensitive manner.

Les prédictions astrologiques annuelles constituent un genre littéraire cohérent qui suscite deplus en plus d’intérêt de la part des historiens du Moyen Âge et de la première modernité. Cettethèse étudie plus particulièrement leur généralisation dans l’Europe latine entre 1405 et 1484,plusieurs siècles après les premières mentions dans les sources théoriques. Une première partieexplore la dialectique interne de ces « jugements », et en particulier les méthodes astrologiques qui,rigoureusement appliquées, soutiennent la prétention scientifique de leurs auteurs. Ceux-ci, leurmilieu social et plus généralement le contexte de production de ces prédictions font l’objet d’unedeuxième partie. Une troisième examine la réception contemporaine et la transmission jusqu’à nosjours de textes pourtant promis à une existence éphémère. Cette étude est complétée et étayée parun catalogue systématique de 111 prédictions manuscrites et 84 incunables rédigées en latin etconservées dans les collections publiques, et des 64 astrologues identifiés comme leurs auteurs.Enfin, les trois prédictions annuelles connues pour 1405, à la fois singulières et caractéristiques,font l’objet d’une édition critique commentée et traduite en français. / Astrological annual predictions form a consistent literary genre. In recent years, interest in thesematerials among Middle Ages and Early Modern Era historians has been increasing. This thesisspecially adresses the spreading of this kind of predictions in Latin-speaking Europe between1405 and 1484, several centuries after they are firstly mentioned in theoretical sources. Our firstpart explores the internal dialectics of these prognostications, and in particular the strictly-followedmethods of astrological calculation provided as support to the authors’ scientific pretensions. Thegeneral context of production, and the social background of these authors, form a second part ofthe thesis. The third part considers the contemporary reception of these astrological predictions,as well as their unlikely transmission until our days in spite of the genre’s ephemeral nature. Acomprehensive catalogue of the 111 handwritten and 84 incunable latin prognostications preservedin public collections, as well as the 64 astrologers potentially identified as their authors, completethis study. Finally, we offer a critical edition, with French translation and commentary, of the threeknown predictions for year 1405 which, in spite of their individual features, constitute model samplesof the genre.

<p>The main purpose of the present study was to obtain an in-depth understanding of what the final phase of life was like for a group of gravely ill and dying cancer patients, with focus on autonomy, dependency and quality of life. The specific aims were to: 1) describe the patients' autonomy and how the attitudes of relatives and staff promoted/hindered patient participation in decision-making, 2) describe how the patients assessed their quality of life in two care cultures, 3) describe how members of the care team prognosticated the patients' remaining survival time, and 4) investigate continuity of care site in two different care cultures during the patients' final month of life. The theoretical framework consisted of Weisman's concept of an appropriate death, and an ethical perspective based on a dialogical ethic and truthfulness.</p><p>The study comprised 56 consecutively selected adult cancer patients. Data was collected via retrospective interviews with relatives, quality of life assessments by the patients, prognoses/motivations from members in the care team, and register data on the utilisation of forms of care. Both qualitative and quantitative methods were used. </p><p>Four categories respecting autonomy were found; the dying patients exercised their autonomy as self-determiners, co-determiners, delegators and nonparticipators. The co-determiners and delegators practised "shared autonomy" in interaction with relatives and staff, and a dialogue characterised by truthfulness was typical of the interplay. In the assessment of quality of life, half of the patients assessed themselves as satisfied/somewhat satisfied with their situation. The "cognitive-" and "emotional functioning" differed least from that of a normal population, while "physical-", "role functioning" and "global health status/quality of life" differed most. The prognosticated and the actual remaining survival time were in agreement for 19/51 patients (± 0.5 months). Some resistance to prognosticating emerged. The members of the care team used different forms of knowledge to motivate their prognostication. Continuity in terms of care site was fairly high for the majority of dying patients. To a great extent, organisational and structural factors determined the choice of care form. </p>

The main purpose of the present study was to obtain an in-depth understanding of what the final phase of life was like for a group of gravely ill and dying cancer patients, with focus on autonomy, dependency and quality of life. The specific aims were to: 1) describe the patients' autonomy and how the attitudes of relatives and staff promoted/hindered patient participation in decision-making, 2) describe how the patients assessed their quality of life in two care cultures, 3) describe how members of the care team prognosticated the patients' remaining survival time, and 4) investigate continuity of care site in two different care cultures during the patients' final month of life. The theoretical framework consisted of Weisman's concept of an appropriate death, and an ethical perspective based on a dialogical ethic and truthfulness. The study comprised 56 consecutively selected adult cancer patients. Data was collected via retrospective interviews with relatives, quality of life assessments by the patients, prognoses/motivations from members in the care team, and register data on the utilisation of forms of care. Both qualitative and quantitative methods were used. Four categories respecting autonomy were found; the dying patients exercised their autonomy as self-determiners, co-determiners, delegators and nonparticipators. The co-determiners and delegators practised "shared autonomy" in interaction with relatives and staff, and a dialogue characterised by truthfulness was typical of the interplay. In the assessment of quality of life, half of the patients assessed themselves as satisfied/somewhat satisfied with their situation. The "cognitive-" and "emotional functioning" differed least from that of a normal population, while "physical-", "role functioning" and "global health status/quality of life" differed most. The prognosticated and the actual remaining survival time were in agreement for 19/51 patients (± 0.5 months). Some resistance to prognosticating emerged. The members of the care team used different forms of knowledge to motivate their prognostication. Continuity in terms of care site was fairly high for the majority of dying patients. To a great extent, organisational and structural factors determined the choice of care form.

Magistro darbe yra išanalizuoti ir susiteminti įvairių Lietuvos ir užsienio autorių teoriniai pelno sampratos ekonomikoje ir apskaitoje aspektai. Pateiktos pelno ir pelningumo rodiklių apskaičiavimo problemos ir analizės metodikos, akcentuojant pagrindinių priežasčių, įtakojančių gautus rezultatus, ištyrimą. Aptarti finansinių prognozių metodai. Atlikta kelių tiesimo ir remonto įmonės pelno ir pelningumo rodiklių struktūros bei dinamikos analizė. Pateiktas gautų rezultatų įvertinimas pagrindinių konkurentų rinkoje bei pramonės šakos atžvilgiu. Atliktas įmonės paklausos sezoniškumo tyrimas. Apibendrinti vidiniai bei išoriniai veiksniai, lėmę įmonės veiklos ekonominius rezultatus. Atliktas įmonės veiklos modeliavimas ieškant pelningiausių sprendimų. Remiantis gautais rezultatais prognozuoti tolimesni veiklos rodikliai. Veiklos rezultatai įvertinti pritaikant ekonominius svertus. Remiantis gautais duomenimis suformuluotos išsamios išvados ir pateikti pasiūlymai įmonės veiklos pelningumo didinimui. / Theoretical aspects of profit concept in economics and accounting of various Lithuanian and foreign authors are analysed and systematized. Profit and profitability index calculation problems and analytical methods are given, stressing research of the main reasons influencing the results obtained. Financial prognostication methods are discussed. Profit and profitability index structures and dynamics analysis are performed for road laying and repair company. Evaluation of the results obtained is given in relation with the main competitors’ market as well as with the industry. Seasonal changes in the demand are analysed for the company. Internal and external factors are summarized, which played a role in the economic results of the company’s performance. Activity modelling is performed for the company, seeking for the most profitable solutions. Basing upon the results obtained, further performance indices are forecasted. Performance results are evaluated using the economic leverage. Basing upon the results obtained, thorough conclusions are formulated, suggestions to improve performance profitability are given.

Background: Early differentiation between transient ischemic attack (TIA) and minor ischemic stroke (MIS) impacts on the patient’s individual diagnostic work-up and treatment. Furthermore, estimations regarding persisting impairments after MIS are essential to guide rehabilitation programs. This study evaluated a combined clinical- and serum biomarker-based approach for the differentiation between TIA and MIS as well as the mid-term prognostication of the functional outcome, which is applicable within the first 24 h after symptom onset. Methods: Prospectively collected data were used for a retrospective analysis including the neurological deficit at admission (National Institutes of Health Stroke Scale, NIHSS) and the following serum biomarkers covering different pathophysiological aspects of stroke: Coagulation (fibrinogen, antithrombin), inflammation (C reactive protein), neuronal damage in the cellular [neuron specific enolase], and the extracellular compartment [matrix metalloproteinase-9, hyaluronic acid]. Further, cerebral magnetic resonance imaging was performed at baseline and day 7, while functional outcome was evaluated with the modified Rankin Scale (mRS) after 3, 6, and 12 months. Results: Based on data from 96 patients (age 64 ± 14 years), 23 TIA patients (NIHSS 0.6 ± 1.1) were compared with 73 MIS patients (NIHSS 2.4 ± 2.0). In a binary logistic regression analysis, the combination of NIHSS and serum biomarkers differentiated MIS from TIA with a sensitivity of 91.8% and a specificity of 60.9% [area under the curve (AUC) 0.84]. In patients with NIHSS 0 at admission, this panel resulted in a still acceptable sensitivity of 81.3% (specificity 71.4%, AUC 0.69) for the differentiation between MIS (n = 16) and TIA (n = 14). By adding age, remarkable sensitivities of 98.4, 100, and 98.2% for the prediction of an excellent outcome (mRS 0 or 1) were achieved with respect to time points investigated within the 1-year follow-up. However, the specificity was moderate and decreased over time (83.3, 70, 58.3%; AUC 0.96, 0.92, 0.91). Conclusion: This pilot study provides evidence that the NIHSS combined with selected serum biomarkers covering pathophysiological aspects of stroke may represent a useful tool to differentiate between MIS and TIA within 24 h after symptom onset. Further, this approach may accurately predict the mid-term outcome in minor stroke patients, which might help to allocate rehabilitative resources.

Le taux de survie des patients souffrant d’un arrêt cardiaque extrahospitalier est inférieur à 10% même avec les meilleures pratiques en réanimation. Une nouvelle technique de réanimation, soit la réanimation par circulation extracorporelle, a été mise à l’essai et s’avère prometteuse pour améliorer le pronostic chez cette population. Par contre, des réponses à plusieurs enjeux doivent être obtenues avant de tester de façon prospective les avantages de cette technique, notamment quant aux impacts collatéraux sur les pratiques de réanimation préhospitalière qu’elle impliquerait, à la sélection des patients et aux potentielles stratégies de monitorage à utiliser chez ces patients. Cette thèse vise à répondre à ces questions avant d’éventuellement démontrer la valeur ajoutée de cette technique de réanimation et ainsi améliorer la survie pour ces patients. Le premier volet présente les résultats de trois études de cohorte explorant les impacts qu’aurait l’incorporation de la réanimation par circulation extracorporelle sur les protocoles de soins. Les résultats d’une première étude de cohorte ont démontré que la durée des manœuvres de réanimation avancées pratiquées en préhospitalier pourrait être réduite pour permettre un départ plus rapide vers un centre hospitalier pouvant initier la réanimation par circulation extracorporelle puisqu’il n’y avait pas d’association positive entre la durée de ces manœuvres et la survie chez ces patients. Les résultats d’une deuxième étude ont démontré que de rediriger les patients en arrêt cardiaque vers les centres hospitaliers pouvant pratiquer la réanimation par circulation extracorporelle pourrait augmenter leur taux de survie. Ce bénéfice potentiel subsistait jusqu’à un ajout de 14 minutes de la durée du trajet par ambulance dû à la redirection. Troisièmement, la modification de ces deux protocoles de soins permettrait à potentiellement trois fois plus de patients de bénéficier d’une réanimation par circulation extracorporelle. Le second volet présente les résultats de deux études visant à optimiser la sélection des patients pour une réanimation par circulation extracorporelle. Les résultats d’une première étude de cohorte descriptive ont démontré que les patients nécessitant plus de 10 défibrillations conservaient un pronostic de survie adéquat, et ainsi devraient demeurer éligible à une réanimation par circulation extracorporelle. Dans une deuxième étude de cohorte, nous avons étudié l’impact pronostique d’une conversion de rythme pendant la réanimation et avons démontré que le rythme initial était un meilleur marqueur de pronostic que la conversion du rythme. Ainsi, les patients ayant une conversion d’un rythme non-défibrillable à un rythme défibrillable ne devraient pas être retenus en première intention pour une réanimation par circulation extracorporelle, contrairement à ceux dont le rythme initial était déjà défibrillable. Les études du troisième volet visaient à explorer l’usage d’une technologie de monitorage de l’oxymétrie tissulaire, la spectroscopie proche-infrarouge, en raison de son potentiel pour mesurer en continu le degré d’oxygénation des candidats à une réanimation par circulation extracorporelle. Une revue systématique de la littérature a démontré l’utilité pronostique de cette technologie pour les patients en arrêt cardiaque. Ensuite, nous avons décrit à l’aide d’une cohorte prospective les propriétés métrologiques de deux appareils et les facteurs associés permettant d’optimiser leur utilité dans le contexte de patients en arrêt cardiaque. Les connaissances développées par l’entremise des études composant la présente thèse ont déjà été intégrées aux protocoles de prise en charge des patients souffrant d’un arrêt cardiaque extrahospitalier ce qui jette des bases solides pour poursuivre des recherches pour ultimement améliorer leur pronostic. / Despite advances in medical care, survival amongst out of hospital cardiac arrest patients remains low, with only 10% of patients surviving. The use of extracorporeal cardiopulmonary resuscitation, a novel resuscitation procedure, has recently garnered interest and showed promise to improve resuscitation outcomes. However, questions remain to be answered before this technology can be prospectively evaluated, notably regarding the collateral impacts of its implementation, appropriate patient selection and the monitoring strategies to use for these patients. The main objective of this thesis is to answer these questions to eventually improve the outcome of patients suffering from an out-of-hospital cardiac arrest. In the first part, the results of three cohort studies exploring the potential impact of the implementation of extracorporeal resuscitation on prehospital resuscitation protocols are presented. A first cohort study showed that the duration of prehospital advanced cardiac life support could be reduced to allow for an earlier transport to an extracorporeal resuscitation centre. A second cohort study showed that patients being transported to specialized resuscitation centres might have increased survival. This increase in survival would remain despite an additional 14 minutes of prehospital transport time due to the redirection. A third study showed that prehospital redirection could triple the number of patients who could benefit from extracorporeal resuscitation. In the second part, the results of two studies aiming to improve the selection of adequate patients for extracorporeal resuscitation are presented. A first cohort study showed that patients requiring more than 10 defibrillations still had an adequate chance at survival and should remain eligible for an extracorporeal resuscitation. A second cohort study showed that the initial rhythm was a much better prognosticating factor than subsequent rhythms. Patients with an initial non- shockable rhythm who experience a conversion to a shockable rhythm should not be considered first-line candidates for extracorporeal resuscitation. In the third part, three studies exploring the potential uses of near-infrared spectroscopy for the monitoring of extracorporeal resuscitation patients are presented. A systematic review was first performed and showed the prognosticating ability of this technology for patients suffering from a cardiac arrest. Then, using a prospective cohort, the metrological properties and their determinants of two frequently used near-infrared spectroscopy devices were described, in order to optimize their uses in the context of cardiac arrest. The knowledge acquired by the studies comprised in this thesis has already been integrated in protocols guiding the care for patients suffering from an out-of-hospital cardiac arrest and has laid the foundation for the prospective evaluation of extracorporeal resuscitation for this population, which will hopefully ultimately lead to improvement in their prognosis.