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.

Introduction: Obstructive sleep apnea (OSA) is a common breathing disorder with numerous health consequences, including greater risk of complications perioperatively. Undiagnosed OSA is known to place surgical patients at a higher risk of serious adverse events, including stroke and death. Polysomnography (PSG) assessment is the current gold standard test for diagnosing OSA. However, due to the significant time commitment and cost associated with PSG, a substantial number of OSA patients go undiagnosed before the perioperative period. Although the STOP-Bang questionnaire screening tool is currently used to help detect OSA patients, the low specificity to screen people without the disease is considered a major limitation. There is a clear need to develop a quick and effective prediction rule with higher overall accuracy to help streamline OSA diagnosis. Tracheal breathing sound analysis in awake patients at the bedside has shown potential to screen OSA patients with higher specificity compared to the STOP-Bang questionnaire. To date, no screening tools exist to detect OSA patients that combine the results of breathing sound analysis and STOP-Bang. Objectives: The present study aimed to develop a prediction rule, using both breathing sound analysis and variables in the STOP-Bang questionnaire, to better streamline the diagnosis of OSA. Methods: This prospective cohort study recruited patients referred for PSG at the Ottawa Hospital Sleep Centre from November 2016 to May 2017. The study conduct was approved by the Ottawa Health Science Network Research Ethics Board (#20160494-01H). After obtaining informed consent, anthropomorphic, breathing sound recordings, and STOP-Bang questionnaire data was collected from over 400 consenting patients. All patients that met the eligibility criteria were included. The breathing sound analysis and STOP-Bang results were utilized to design a prediction rule using logistic regression. Sensitivity, specificity, and likelihood ratio were used to compare the diagnostic performance of the final model. Results: Of the 439 consenting study participants, 280 study participants data were eligible for inclusion in the logistic regression analysis. Physician sleep specialists diagnosed 114 participants (41%) with moderate-to-severe OSA and 166 participants (59%) with normal-to-mild OSA. At a predicted probability of moderate-to-severe OSA greater than or equal to 0.5, breathing sound analysis had a similar sensitivity of 75.9 (95%CI; 65.4, 82.0) and higher specificity of 74.5% (95%CI; 68.5, 82.0) when compared to STOP-Bang with a sensitivity and specificity of 68.4% (95%CI; 58.9, 76.6) and 63.2% (95%CI: 55.0, 70.1), respectively. The sensitivity and specificity for the Safe-OSA rule, obtained by combining breathing sound analysis and STOP-Bang variables, were determined to be 75.4% (95%CI; 65.4, 82.0) and 74.5% (95%CI; 68.5, 82.0), respectively. A sensitivity analysis using a likelihood ratio test showed that breathing sound analysis contributed significantly to the performance of the Safe-OSA rule. The Safe-OSA rule was determined to be reasonably discriminative and well calibrated. The five-fold cross-validation showed similar results for the final model in the derivation and testing subsamples, which provides support for the internal validity of the Safe-OSA rule in our study population. Conclusion: The present study lends further support for the future testing of tracheal breathing sound analysis as a potential method to screen for moderate-to-severe OSA to help streamline patient care in the perioperative setting. Trial registration: ClinicalTrials.gov identifier NCT02987283.

The goal of this study was to derive a clinical prediction rule for transient ischemic attack (TIA) and non-disabling stroke to predict a treatment change based on echocardiogram. Methods: We conducted a cohort sub-study for TIA and non-disabling stroke patients collected over five years from 8 Emergency Departments. We compiled a list of 27 potential predictors to look for treatment change based on echocardiogram findings. We used a univariate, logistic regression and recursive partitioning analysis to develop the final prediction model. Results: The frequency of treatment change was seen in 87 (3.1%) of 2804 cases. The final model contains six predictors: age less than 50 years old, coronary artery disease history, history of heart failure, any language deficit, posterior circulation infarct and middle cerebral artery infarct on neuroimaging. Conclusions: We have developed a highly sensitive clinic prediction rule to guide in the use of echocardiogram in TIA and non-disabling stroke.

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.