京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第20624号 / 社医博第82号 / 社新制||医||9(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 木原 正博, 教授 古川 壽亮, 教授 柳田 素子 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

Background - Current guidelines suggest that all cancer patients with venous thrombosis be treated with long-term low molecular weight heparin. Whether treatment strategies should vary according to clinical characteristics remains unknown. // Systematic review - A systematic review was performed to determine current understanding of the association between malignancy characteristics in patients with cancer-associated VTE and the risk of VTE recurrence. Four retrospective and 6 prospective studies were included. They suggest that lung cancer, metastases, and adenocarcinomas confer an increased the risk of recurrence and breast cancer a low risk. // Survey - I performed survey to evaluate thrombosis experts’ opinion about the low risk of VTE recurrence they would consider acceptable for patients with cancer- associated thrombosis 103 specialists participated. 80% of respondents agreed that a risk of recurrent VTE during anticoagulation below 7% is low enough. 92% agreed that a CPR that categorizes risk of recurrence is relevant. // Retrospective Study - I performed a single retrospective cohort study to assess the feasibility of derivation of a CPR that stratifies VTE recurrence risk in patients with cancer–associated thrombosis. The study included 543 patients. A multivariate analysis selected female, lung cancer and prior history of VTE as high risk predictors and breast cancer and stage I disease as low risk. // Conclusion - Patients with cancer-associated thrombosis do have varying risks of recurrent VTE depending on clinical characteristics.

Background - Current guidelines suggest that all cancer patients with venous thrombosis be treated with long-term low molecular weight heparin. Whether treatment strategies should vary according to clinical characteristics remains unknown. // Systematic review - A systematic review was performed to determine current understanding of the association between malignancy characteristics in patients with cancer-associated VTE and the risk of VTE recurrence. Four retrospective and 6 prospective studies were included. They suggest that lung cancer, metastases, and adenocarcinomas confer an increased the risk of recurrence and breast cancer a low risk. // Survey - I performed survey to evaluate thrombosis experts’ opinion about the low risk of VTE recurrence they would consider acceptable for patients with cancer- associated thrombosis 103 specialists participated. 80% of respondents agreed that a risk of recurrent VTE during anticoagulation below 7% is low enough. 92% agreed that a CPR that categorizes risk of recurrence is relevant. // Retrospective Study - I performed a single retrospective cohort study to assess the feasibility of derivation of a CPR that stratifies VTE recurrence risk in patients with cancer–associated thrombosis. The study included 543 patients. A multivariate analysis selected female, lung cancer and prior history of VTE as high risk predictors and breast cancer and stage I disease as low risk. // Conclusion - Patients with cancer-associated thrombosis do have varying risks of recurrent VTE depending on clinical characteristics.

Background - Current guidelines suggest that all cancer patients with venous thrombosis be treated with long-term low molecular weight heparin. Whether treatment strategies should vary according to clinical characteristics remains unknown. // Systematic review - A systematic review was performed to determine current understanding of the association between malignancy characteristics in patients with cancer-associated VTE and the risk of VTE recurrence. Four retrospective and 6 prospective studies were included. They suggest that lung cancer, metastases, and adenocarcinomas confer an increased the risk of recurrence and breast cancer a low risk. // Survey - I performed survey to evaluate thrombosis experts’ opinion about the low risk of VTE recurrence they would consider acceptable for patients with cancer- associated thrombosis 103 specialists participated. 80% of respondents agreed that a risk of recurrent VTE during anticoagulation below 7% is low enough. 92% agreed that a CPR that categorizes risk of recurrence is relevant. // Retrospective Study - I performed a single retrospective cohort study to assess the feasibility of derivation of a CPR that stratifies VTE recurrence risk in patients with cancer–associated thrombosis. The study included 543 patients. A multivariate analysis selected female, lung cancer and prior history of VTE as high risk predictors and breast cancer and stage I disease as low risk. // Conclusion - Patients with cancer-associated thrombosis do have varying risks of recurrent VTE depending on clinical characteristics.

This project set out to derive a prediction rule based on preoperative clinical variables to identify patients with high risk of developing atrial fibrillation following cardiac surgery. Methods: Prospectively collected data from a perioperative database was corroborated with chart review to identify eligible patients who had non-emergent surgery in 2010. Details on 28 preoperative variables were collected and significant predictors (p<0.2) were inserted into multivariable logistic regression and recursive partitioning. Results: 305 (30.5%) of 999 patients developed new onset postoperative atrial fibrillation. Eleven variables were significantly associated with atrial fibrillation, however, both final models included only three: left atrial dilatation, mitral valve disease and age. Bootstrapping with 5000 samples confirmed that both final models provide consistent predictions. Coefficients from the logistic regression model were converted into a simple seven point predictive score. Conclusions: This simple risk score can identify patients at higher risk of developing atrial fibrillation after cardiac surgery.

Background - Current guidelines suggest that all cancer patients with venous thrombosis be treated with long-term low molecular weight heparin. Whether treatment strategies should vary according to clinical characteristics remains unknown. // Systematic review - A systematic review was performed to determine current understanding of the association between malignancy characteristics in patients with cancer-associated VTE and the risk of VTE recurrence. Four retrospective and 6 prospective studies were included. They suggest that lung cancer, metastases, and adenocarcinomas confer an increased the risk of recurrence and breast cancer a low risk. // Survey - I performed survey to evaluate thrombosis experts’ opinion about the low risk of VTE recurrence they would consider acceptable for patients with cancer- associated thrombosis 103 specialists participated. 80% of respondents agreed that a risk of recurrent VTE during anticoagulation below 7% is low enough. 92% agreed that a CPR that categorizes risk of recurrence is relevant. // Retrospective Study - I performed a single retrospective cohort study to assess the feasibility of derivation of a CPR that stratifies VTE recurrence risk in patients with cancer–associated thrombosis. The study included 543 patients. A multivariate analysis selected female, lung cancer and prior history of VTE as high risk predictors and breast cancer and stage I disease as low risk. // Conclusion - Patients with cancer-associated thrombosis do have varying risks of recurrent VTE depending on clinical characteristics.

This project set out to derive a prediction rule based on preoperative clinical variables to identify patients with high risk of developing atrial fibrillation following cardiac surgery. Methods: Prospectively collected data from a perioperative database was corroborated with chart review to identify eligible patients who had non-emergent surgery in 2010. Details on 28 preoperative variables were collected and significant predictors (p<0.2) were inserted into multivariable logistic regression and recursive partitioning. Results: 305 (30.5%) of 999 patients developed new onset postoperative atrial fibrillation. Eleven variables were significantly associated with atrial fibrillation, however, both final models included only three: left atrial dilatation, mitral valve disease and age. Bootstrapping with 5000 samples confirmed that both final models provide consistent predictions. Coefficients from the logistic regression model were converted into a simple seven point predictive score. Conclusions: This simple risk score can identify patients at higher risk of developing atrial fibrillation after cardiac surgery.

Anterior knee pain (AKP) is a common, chronic lower limb musculoskeletal overuse condition that represents substantial morbidity to those affected, and has a significant impact on the health care industry. Health practitioners frequently prescribe foot orthoses in the management of AKP as an alternative or adjunct to multimodal physiotherapy. The primary aim of this thesis was to investigate the clinical efficacy of foot orthoses in AKP, utilising high-quality research methodologies. The two systematic reviews conducted have identified a significant gap in the literature regarding evidence from randomised clinical trials (RCTs) for foot orthoses in AKP and other lower limb overuse conditions. While the best evidence for AKP management was for multimodal physiotherapy, there was insufficient evidence to support or refute the use of foot orthoses in the treatment of lower limb overuse conditions, including AKP. Meta-analysis provided evidence to support the use of foot orthoses in the prevention of the first incidence of lower limb overuse conditions. An interesting finding was evidence from pooled and individual study data of no difference between custom and prefabricated foot orthoses in both treatment and prevention of lower limb overuse conditions, inferring that either type of orthosis may be utilised. Both systematic reviews highlighted substantial methodological flaws of the included studies, and recommended that future studies include larger participant numbers, longer participant follow-up, more consistent use of reliable and valid outcome measures and reporting of outcome data, and utilisation of the CONSORT guidelines in the design and reporting of RCTs. A 12-month prospective RCT investigated the short- and long-term clinical efficacy of prefabricated foot orthoses in the treatment of 179 participants with AKP. Foot orthoses were more effective than flat shoe inserts in the short term, implying that their contoured form has some therapeutic effect. Foot orthoses were not significantly different to multimodal physiotherapy over 12 months, nor was there any benefit in adding foot orthoses to physiotherapy. Considering that all groups experienced clinically meaningful long-term improvements in pain and function, clinicians may prescribe foot orthoses for AKP to hasten recovery. Findings of post-hoc analyses to develop a clinical prediction rule indicate that those of older age and shorter height, who have a lower severity of AKP and a more mobile midfoot, are more than twice as likely to experience a successful outcome with foot orthoses. As a secondary aim, this thesis has provided a more comprehensive profile of AKP as a condition. Baseline data from the RCT participants confirms previous reports of higher rates of AKP in females, and a tendency towards bilaterality and chronicity. This AKP sample did not differ from asymptomatic individuals in terms of body mass index, physical activity level, general and mental health, and foot posture, although they tended to have a more mobile foot under load. These characteristics tend to be homogenous across a number of published RCTs, indicating that the findings of the RCT described above are likely to be generalisable to the broader population with AKP. An additional finding in this group was that those with AKP of long duration, higher pain levels, lower functional levels, and an overall lower score on a specific measure of AKP have a poorer prognosis over 12 months, irrespective of their age, gender or morphometry. These findings suggest that, in order to improve prognosis and the chance of a successful outcome, the primary goals of intervention should be to reduce the severity and duration of AKP, through the use of early intervention with foot orthoses, multimodal physiotherapy, or a combination of the two.

Les algies pelviennes aigues constituent le premier motif de consultation aux urgences gynécologiques. Les étiologies possibles de ces algies pelviennes aigues sont nombreuses et incluent à la fois des affections gynécologiques et non gynécologiques. Certaines de ces affections peuvent, en l’absence de diagnostic précoce et d’un traitement adapté, avoir des conséquences très graves. Dans ce travail, nous avons développé un autoquestionnaire standardisé de manière qualitative dédié aux urgences gynécologiques par des entretiens structurés. Nous avons ensuite construit des modèles de prédiction clinique dédiés (i) au diagnostic de rupture tubaire chez les patientes porteuses de grossesses extra-utérines et (ii) au diagnostic de torsion d’annexe à partir de cet autoquestionnaire. Après avoir défini le concept d’urgence potentiellement à risque en gynécologie, nous avons proposé (iii) un modèle de prédiction clinique de celles-ci basé sur notre autoquestionnaire standardisé. A l’issue du développement de ces modèles, nous avons sélectionné certains items de l’autoquestionnaire standardisé afin d’en proposer une version simplifiée. L’utilisation de nos modèles pour le tri et le diagnostic des patientes aux urgences gynécologiques pourrait permettre d’optimiser la prise en charge des patientes. Dans les groupes à haut risque de pathologie, les patientes pourraient bénéficier d’une prise en charge plus rapide avec une éventuelle diminution de la morbidité secondaire à la pathologie. Pour les patientes classées à bas risque, une désescalade des examens complémentaires et des chirurgies inutiles pourrait aussi permettre une diminution de la morbidité d’origine iatrogène. / Acute pelvic pain is the main reason for emergency gynecologic consultation. The possible etiologies of acute pelvic pain are numerous and include both gynecological and non gynecological diseases. Some of these conditions may, in the absence of early diagnosis and appropriate treatment, have very serious consequences. In this work, we developed qualitatively a standardized self-assessed questionnaire dedicated to gynecological emergencies by structured interviews. We then developed clinical prediction rules for (i) the diagnosis of tubal rupture in patients who have ectopic pregnancies and (ii) the diagnosis of adnexal torsion. After a definition of the concept of potentially at risk emergencies in gynecology, we have proposed (iii) a clinical prediction rule based on our questionnaire. Following the development of these models, we selected items from the self-assessed questionnaire in order to propose a simplified version. Using our models for triaging and diagnosis of patients with gynecologic emergencies may optimize the management of patients. In groups at high risk of disease, patients may benefit from faster medical management with a possible decrease in morbidity. For patients classified as low risk, decrease of complementary tests and unnecessary surgery could also allow a reduction of iatrogenic morbidity.

Une lésion médullaire traumatique (LMT) a des conséquences neurologiques importantes, dont l’altération de la capacité à marcher. Prédire précocement cette capacité suite au traumatisme a inspiré le développement de multiples règles de prédiction. Simples et précises, elles prédisent la marche intérieure sur de courtes distances, sans considérer la qualité de la marche. L’utilité et la valeur ajoutée de ces règles n’ont jamais été évaluées comparativement au jugement non structuré des cliniciens à qui elles sont dédiées. L’objectif était d’identifier des éléments de l’évaluation aiguë standardisée ISNCSCI (International Standards for Neurological Classification of Spinal Cord Injury) permettant de développer une règle de prédiction clinique pour la marche communautaire extérieure indépendante un an après une LMT, tout en assurant une bonne validité externe et une utilité clinique lorsque comparée au jugement des cliniciens. La force segmentaire du membre inférieur le plus fort et la préservation de la sensibilité au toucher léger sont de meilleurs prédicteurs d’une marche indépendante. Une règle de prédiction clinique a également pu être développée : elle est pertinente; généralisable; simple; tient compte de la qualité de la marche; et est axée sur la vie communautaire, la participation sociale et la qualité de vie. La performance d’une règle de prédiction de la marche intérieure est statistiquement similaire à celle de cliniciens utilisant leur jugement non structuré, mais peut varier. Cette recherche recommande l’utilisation de règles de prédiction clinique comme aide à la décision chez les patients après une LMT, dont celle développée pour la marche communautaire indépendante. / Traumatic spinal cord injury (TSCI) has important neurological consequences including impaired walking ability. Predicting early the ability to walk again after the trauma has inspired the development of multiple clinical prediction rules. Simple and accurate, they do predict walking on short indoor distances but do not consider the quality of walking. Moreover, the usefulness and added value of these rules have never been evaluated and compared to the unstructured clinical judgment of the physicians for whom they are intended. The objective of this thesis was to identify elements of the acute INSCSCI (International Standards for Neurological Classification of Spinal Cord Injury) standardized evaluation that would allow the development of a clinical prediction rule for outdoor independent community walking one year after a TSCI, ensuring good internal and external validity as well as clinical usefulness when compared to clinical judgment. The strength of the strongest lower limb and preserved light touch sensation are the best predictors of independent walking. A clinical prediction rule was developed to meet the objective: this rule is relevant; generalizable; simple; takes into consideration the quality of walking; and is focused on community living, social participation and quality of life. The performance of a clinical prediction rule for indoor walking is statistically similar to that of clinicians using their unstructured judgment, but can vary depending on different factors. This research recommends the use of clinical prediction rules as a decision aid in patients who have undergone a TSCI, including the one developed for independent functional community walking.