京都大学 / 新制・論文博士 / 博士(医学) / 乙第13599号 / 論医博第2309号 / 新制||医||1072(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 山本 洋介, 教授 近藤 尚己, 教授 西浦 博 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Submitted in partial compliance with the requirements for the Master’s Degree in Technology: Chiropractic, Durban University of Technology, 2014. / Flexion distraction chiropractic technique (FDCT) is a commonly used manual therapy technique which is purported to address various clinical pain syndromes. However, it lacks the credibility of appropriate evidence-based guidelines. An analysis of the literature would be able to inform the development of guidelines. Objectives: The aim of this systematic review was to determine the evidence to support the use of FDCT in clinical practice. Data sources: A systematic review of PubMed and Summons was conducted, using the following search terms: chiropractic, flexion distraction, protocol and / or technique. Study selection: All electronic or paper, English articles, which possessed the required key indexing terms and represented randomised and non-randomised controlled study designs were included. Data extraction: Blinded review of the articles was conducted by three independent reviewers utilising the PEDro (for randomised controlled trials) and NOS for (non-randomised controlled trials). This allowed the methodological rigour of the article to be ranked. This ranking was compared to a critical appraisal of the article in order to achieve an overall decision with regards to the contribution of the article to the level of evidence for FDCT. Data synthesis: 18 review outcomes were aggregated around four clinical categories; two articles each on neck pain, chronic pelvic pain, and physiological outcomes and the remaining twelve on low back pain. There was agreement that the evidence for pelvic pain and physiological function was limited to no evidence and limited respectively. Conflicting evidence existed for neck and low back pain (single and multimodal treatment) with limited and moderate evidence respectively. Conclusion: FDCT is clinically advocated for many conditions. The evidence provided in this review indicates that practitioners should be guarded in their use of FDCT, as the evidence to its widespread use is limited to only those conditions noted in this review. Therefore, further high quality and rigorous studies are required to develop appropriate treatment guidelines for use by practitioners to adequately provide evidence based care in clinical practice.

Background: Breast cancer is the most frequently diagnosed cancer and a leading cause of cancer death among females, both worldwide and in the UK. Although, UK incidence of breast cancer is rising, breast cancer mortality rates are falling, due largely to early detection and improved treatment. As a result there are more women living with a diagnosis of breast cancer than ever before. Due mainly to side-effects of adjuvant therapy, breast cancer patients may require diagnostic, therapeutic, supportive or palliative services many years post-diagnosis, which poses a major challenge to already stretched healthcare services. Accordingly, effective and inexpensive interventions that can alleviate treatment side-effects, improve health, quality of life and potentially reduce risk of early mortality are required for breast cancer patients. Awareness of the positive influence that physical activity can have on breast cancer development and outcome is an important determinant of physical activity levels. A higher level of physical activity before and after breast cancer diagnosis is related to a lower risk of all-cause and breast cancer-related mortality. Randomised controlled trials have reported beneficial effects of physical activity interventions on outcomes relating to health, quality of life and mortality risk among breast cancer survivors. Aims: The present project aimed to: 1) assess awareness of the role of physical activity on breast cancer risk and the sufficiency of physical activity undertaken in women attending the NHS breast screening programme (NHSBSP), 2) compare physical activity levels of women at different stages of breast cancer pathway, 3) investigate the effects of a low-cost six-month home-based physical activity intervention on physical activity, body mass, health-related quality of life (HRQoL), insulin resistance and blood lipid profiles of breast cancer survivors and 4) assess the effects of our home-based intervention on cardiorespiratory fitness in a subset of breast cancer survivors. Methods: A total of 309 volunteers (188 NHSBSP attendees, 41 breast cancer patients undergoing chemotherapy and 80 post-treatment breast cancer survivors) participated in the current project. Physical activity was assessed via the International Physical activity Questionnaires (IPAQ). In studies one and two, Body mass and body mass index (BMI) were assessed directly in chemotherapy patients and breast cancer survivors, and indirectly from self-reported values in NHSBSP attendees. While in study three, body fat percentage was measured via bioelectrical impedance analysis, HRQoL was assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire and fasting blood samples were taken to measure lipid, glucose and insulin concentrations at baseline and post-six month home-based physical activity intervention. In study four, a random subsample of 32 breast cancer survivors undertook an exercise tolerance test to establish peak oxygen uptake values. Results: A high proportion (70%) of NHSBSP attendees engaged in low-moderate levels of physical activity and performed low amounts of recreational physical activity. Attendees demonstrated high awareness (75%) of the role of physical activity in reducing breast cancer risk but those categorised as “low activity” were significantly unaware of insufficiency of activity (p<0.05). Chemotherapy patients and breast cancer survivors had significantly lower levels of total physical activity than NHSBSP attendees (p<0.001 and p<0.05, respectively). The randomised controlled trial revealed significant improvements in total physical activity, body mass (p<0.05), BMI (p<0.05) HRQoL (breast cancer subscale, p<0.01; trial outcome index, p<0.05) and total (p<0.01) and low-density lipoprotein (p<0.05) cholesterol concentrations in the intervention group compared to usual care, and significant improvements in cardiorespiratory fitness (p<0.05) in a subsample of breast cancer survivors allocated to intervention. Conclusions: Physical activity interventions that incorporate strategies aimed at increasing awareness of recommended physical activity guidelines may be required in populations at risk of breast cancer. A relatively large proportion of women at risk of breast cancer may not be sufficiently exposed to the potential benefits of physical activity on breast cancer outcomes. Post-treatment breast cancer patients may be more receptive to physical activity interventions as the negative effects of chemotherapy begin to resolve, and therefore, may benefit from physical activity interventions. Results suggest that a low-cost home-based physical activity intervention with counselling and telephone support can improve the health and HRQoL of breast cancer survivors, which may in turn potentially reduce risk of breast cancer and cardiovascular disease-related mortality. Given the encouraging results and its highly portable and feasible nature, our intervention represents a promising tool for use in health and community settings to benefit large numbers of breast cancer survivors. The current project supports the inclusion of physical activity promotion as an integral component for the management and care of breast cancer survivors.

Motivation: Cardiovascular heart disease (CVD) is the leading cause of death worldwide. Risk markers for CVD include, amongst others, the haemostatic factors tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1), factor VII (FVII) and fibrinogen and more recently, C-reactive protein (CRP), a sensitive marker of inflammation. Epidemiological studies have demonstrated an inverse association between dietary fibre (DF) consumption and risk factors for CVD and CVD prevalence. Some research indicates that this protection may be related to favourable changes in the haemostatic profile and inflammatory markers. This is applicable for the consumption of total DF, as well as soluble and insoluble fibre. However, clinical intervention trials report conflicting data on the effects of DF on t-PA, PAI-1, FVII, fibrinogen and CRP. In addition, available literature is not clear on the mechanisms through which DF may have favourable effects. Objective: The main objective of this study was to review the results of randomised controlled trials systematically on the effects of DF on the above-mentioned selected haemostatic variables and CRP in healthy adults and subjects with hypertriglyceridaemia and the metabolic syndrome. Methods: Human adult intervention trials, at least two weeks in duration, with an increased and measurable consumption of DF were included. Electronic databases were searched from the earliest record to May/July 2006 and supplemented by crosschecking reference lists of relevant publications. From the literature search, two reviewers identified studies that were rated for quality based on the published methodology. No formal statistical analysis was performed due to the large differences in the study designs of the dietary intervention trials. The primary outcome measures were percentage changes between intervention and control groups, or baseline to end comparisons for t-PA, PAI-1, FVII, fibrinogen and CRP. Results t-PA activity increased significantly (14-167%) over the short and long-term following increased fibre intakes. PAI-1 activity decreased significantly between 15-57% over periods ranging from two to six weeks. These favourable changes in t-PA and PAI-1 occurred in healthy, hypertriglyceridaemic and metabolic syndrome subjects following consumption of diets containing ≥3.3 g/MJ DF and ≥4.5 g/MJ DF respectively. Mechanisms through which DF may affect t-PA and PAI-1 include its lowering effect on insulinaemic and glycaemic responses, decreasing triglycerides which are a precursor of very-low-density lipoproteins, fermentation of DF to short-chain fatty acids, which may reduce free fatty acid concentrations, as well as the role of DF in promoting weight loss. High DF intakes did not have a significant effect on fibrinogen concentrations possibly because of relatively little weight loss, too low DF dosages and maintaining a good nutritional status. Inadequate study designs deterred from meaningful conclusions. Significant decreases in FVll coagulant activity (6-16%) were observed with DF intakes of ≥3.3 g/MJ and concomitant decreased saturated fat intakes and weight loss in healthy and hypertriglyceridaemic subjects. Confounding factors include weight loss and a simultaneous decreased intake of saturated fats. The type of fibre seems to play a role as well. Mechanisms through which DF may reduce FVll concentrations include its effects on triglyceride-rich lipoproteins, insulin and weight loss. Increased DF consumption with dosages ranging between 3.3-7.8 g/MJ were followed by significantly lower CRP concentrations (25-54%), however, simultaneous weight loss and altered fatty acid intakes were also present in all the studies. Mechanisms are inconclusive but may involve the effect of DF on weight loss, insulin, glucose, adiponectin, interleukin-6, free fatty acids and triglycerides. Conclusions: Epidemiological evidence indicates an association between DF and the CVD risk factors t-PA, PAI-1, FVII, fibrinogen and CRP. In general, the risk of CVD may improve with high-fibre intakes as indicated by the favourable changes in some of the parameters. However, simultaneous reduced fat intakes and weight loss presented difficulties in separating out the effects of specific components. Furthermore, DF is consumed in a variety of different forms and different dosages that may have different effects. Overall, the study designs used in the intervention trials prevented significant conclusions. DF did, however, play a role in modifying t-PA, PAI-1, FVII and CRP. Potential effects on fibrinogen were not quantifiable. Recommendations: The results from this investigation provide the motivation for additional controlled clinical research to establish the effect and mechanisms of DF on haemostatic variables and CRP. A critical aspect of future studies would be to set up suitable protocols. The amount of subjects, duration of the trials, confounding factors such as weight loss and altered fat intakes and differentiation between types and dosage of DF are important. DF supplemental studies are recommended as they may be the most suitable method to reach meaningful conclusions. / Thesis (Ph.D. (Nutrition))--North-West University, Potchefstroom Campus, 2007

This thesis addresses the question of the design, production and use of information graphics in health technology assessment (HTA). Drawing on previous research in both information design and health policy, it describes a comprehensive design process for creating new visual presentations that can inform health policy-makers. The thesis begins by introducing, and functionally defining the terms ‘information graphics’ and ‘health technology assessment’ in Chapter 1. It then offers a methodological discussion of how research can be performed at the intersection between these two diverse fields. This discussion forms Chapter 2 of the thesis. The context of use is surveyed in two studies, which are presented in Chapter 3. These assess the current use of information graphics in HTA, and the information needs of health policy decision-making bodies. This enables a needs-based approach to the design of 10 information graphics, that could be used in hta. These are shown in Chapter 4. Finally, two of these information graphics are empirically tested with two further research studies, forming Chapter 5 and Chapter 6. The thesis is aimed at giving practical advice to those wanting to produce graphical presentations of information in HTA, and to provide the foundation for further original research in information design and HTA. Chapter 7 draws together the research from the rest of the thesis, to make recommendations in light of the combined findings.

Gliome stellen mit 30-40 % die häufigsten intrakraniellen Tumoren dar. Darunter ist das Glioblastom, auch als Glioblastoma multiforme bezeichnet, mit ca. 50 % am stärksten vertreten und macht somit allein etwa 20 % aller Hirntumoren aus (Russell und Rubinstein 1989). Neben einer Metastasierung über den Liquor können diese Tumoren auch sehr selten als primäre Neubildung im Rückenmark vorkommen. Ebenso ist dort die Entwicklung eines sekundären Glioblastoms aus dem fortschreitenden Wachstum eines niedriggradigen Astrozytoms heraus möglich (Sure et al. 1997). Aufgrund ihres diffus infiltrativen Wachstums sowie der infausten Prognose wird das Glioblastom in der WHO-Klassifikation dem Tumorgrad IV zugeordnet (Louis et al. 2007). Ziel dieser vorliegenden medizinischen Dissertation ist es, mit Hilfe einer Meta-Analyse individueller Patientendaten einen integrativen Überblick über die bereits vorhandene Forschung dieser seltenen Erkrankung zu erlangen. Aus einer umfangreichen Literaturrecherche resultierten 82 geeignete Publikationen, sodass von insgesamt 157 Patienten unter anderem Daten zum Veröffentlichungszeitraum, Alter und Geschlecht des Patienten, Tumorbiologie und –lokalisation sowie Therapie und Outcome erhoben werden konnten. In der statistischen Auswertung wurde die Korrelation dieser Faktoren eingehend untersucht mit dem Ziel, signifikante Aspekte herauszufiltern, die das Überleben von Patienten mit spinalem Glioblastom positiv beeinflussen können. Trotz einer stetigen Verbesserung der bildgebenden Diagnostik durch Magnetresonanztomographie und Computertomographie sowie multimodaler Tumortherapie zeigte sich in der Auswertung der Ergebnisse, dass das mediane Überleben der Patienten mit spinalem Glioblastom bzw. Gliosarkom auf nur rund neun Monate zu beziffern ist. Dabei konnten sowohl das Alter bei Diagnosestellung als auch das Jahr der Veröffentlichung der jeweiligen Patientenfälle als statistisch signifikante und somit bedeutende prognostische Faktoren im Hinblick auf die Überlebenszeit der Patienten identifiziert werden.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / The role of enzyme‐assisted subcutaneous fluid administration (EASFA) in treating mild to moderate dehydration in pediatrics, geriatrics, and palliative care has been studied in developed countries. However, it has historically been underutilized due to widely available health care and alternative treatments, namely peripheral intravenous (IV) fluid administration. Fluid infusions in the subcutaneous tissue have a low risk of infection, are easy to administer, and have wide potential use. The use of EASFA in low resource settings to treat those with difficult IV access or where skilled healthcare workers are not as readily available could prove to be a live saving measure in many situations, including the care of patients in remote areas of the world, mass casualty events, or other disasters. Our objective was to determine if EASFA is a valid and appropriate technique to utilize in pediatric and elderly patients, and evaluate if it could be a safe and efficient way to provide fluid resuscitation in low resource settings. For this systematic review MEDLINE and Cochrane Library were searched from January 1950 to December 2015 to recover all available literature relevant to this topic. Studies that met the inclusion criteria were analyzed using Cohen’s D. This was calculated using the mean difference between intervention and control divided by the pooled standard deviation. For dichotomous outcome of the placement success rate the odds ratios were calculated with 95% confidence intervals. In reviewing 7 articles using Cohen’s D to compare mean differences to determine effect size, we found that catheter placement success rates and infusion rates were similar between EASFA and peripheral intravenous fluid administration. Additionally, it was found that the odds of correct initial needle placement was 7.19 times higher in EASFA versus intravenous administration. EASFA is a comparable alternative to intravenous fluid administration when delivering fluids to pediatric and elderly patients with mild to moderate dehydration. While infusion rates and total volume of fluids administered were similar, the high rate of success with placement of the subcutaneous catheter proves it to be more useful in some situations. Venous cannulation is difficult, even for a trained healthcare provider, and the ease of placement of subcutaneous catheters makes training lay people to administer subcutaneous fluids a possibility. Additionally, this type of fluid administration may lead to less psychological trauma to a child from multiple needle sticks, while still achieving a similar outcome of effective volume replacement. Based on the results of this study, further research is needed to evaluate the effectiveness of utilizing EASFA in low resource settings.

Young women are particularly vulnerable to HIV. Despite the successful HIV prevention efforts in Thailand in the past, young Thai women are at increased HIV risk and in urgent need of effective HIV interventions. Numerous studies have emphasised the importance of family in determining young people’s sexual behaviour. This thesis explores the roles of family in shaping young people’s sexual decisions and examines the potential of family-involved HIV interventions (FIHIs) for young Thai women. The thesis systematically examines studies across settings to determine whether involving family in HIV interventions could influence young people’s sexual behaviour. The findings suggest that FIHIs have a potential in shaping young people’s condom use practices. It identifies several key characteristics of effective FIHIs that can potentially be valuable for future HIV development in other contexts. Qualitative data collected from focus groups of young Thai women in Bangkok are analysed using the framework developed from the systematic review of qualitative studies. The findings highlight several challenges for future FIHIs for young Thai women. These are barriers to parent-child communication, a tension of coexistence of two divergent sexual norms - traditional/Thai versus modern/globalised, alternative sources of sexual health and HIV knowledge, the importance of family relationships, and the different circumstances and needs of young Thai women from different backgrounds. Future FIHIs for young Thai women should consider a comprehensive, structural and eco-developmental approach, simultaneously targeting both individuals and the wider environment. This thesis offers a new contribution to the HIV prevention and sexual health education literature and identifies the potential effectiveness of FIHIs tailored to young Thai women,constituting an important step in addressing the public health problems of HIV/AIDS infections in Thailand.

This thesis presents an empirical investigation into substance use, situational characteristics and sexual outcomes in men who have sex with men (MSM) motivated by the high rates of substance use in MSM; the association between substance use and sexual risk behaviours in MSM; the lack of specific theory addressing relationships between substance use, sexual interactions and social interactions between MSM; and the need for clearer understandings of encounter-level associations with sexual risk. Qualitative metasynthesis. This thesis begins with laying the methodological groundwork for a qualitative metasynthesis that theorises the relationship between substance use and social spaces in MSM, with a particular focus on sexual outcomes. The qualitative metasynthesis derives the key organising perspective of ‘littoral spaces’ in which substance use is associated with a pre-planned, though temporary, escape from the boundaries of everyday life to engage in maximal sensory exploration, including through sexual contact. <b>Systematic review of multiple-event analyses. The thesis then turns to a systematic review of previous quantitative multiple-event analyses examining associations between situational characteristics and sexual outcomes, which establishes the need for additional multiple-event analyses addressing specific substance use, location of sex, partner serodiscordance and partner type. Multiple-event analyses. Finally, informed by the qualitative metasynthesis and the systematic review of event-level analyses, this thesis presents multiple-event analyses addressing unprotected anal intercourse (UAI), pleasure and control as sexual outcomes in MSM in England. These analyses found that substance use was associated with greater odds of UAI and pleasure, but not with control, and that non-private locations of sex were associated with decreased odds of UAI and pleasure, but not control. Furthermore, there was sparse evidence of interactions between respondent and partner substance use and between respondent substance use and location of sex in associations with sexual outcomes. These analyses contribute to understandings of associations between substance use, situational characteristics and sexual risk behaviour by presenting the first known analyses on MSM in England and by examining sexual outcomes besides UAI.